Table 5. [Notable Pathogenic Variants in Genes Causing Nonketotic Hyperglycinemia]. - GeneReviews®

Gene ¹	Reference Sequences	DNA Nucleotide Change (Alias ²)	Predicted Protein Change	Comment [References]
AMT	NM_000481.2 NP_000472.2	c.317T>C	p.Ile106Thr	Founder variant in the Netherlands w/residual GCS activity [Swanson et al 2015]
c.2T>C	p.Met1?	Common variant; assumed no activity [Swanson et al 2015]
c.959G>A	p.Arg320His	Common variant w/no residual GCS activity [Coughlin et al 2017]
c.217C>T	p.Arg73Cys	Common variants [Coughlin et al 2017]
c.280C>T	p.Arg94Trp
NM_000481.2	c.471+2T>C	--
NM_000481.2 NP_000472.2	c.664C>T	p.Arg222Cys
NM_000481.2	c.878-1G>A	--
NM_000481.2 NP_000472.2	c.887G>A	p.Arg296His
c.921G>A	p.Val307Val	Common variant; creates new splice site [Coughlin et al 2017]
GLDC	NM_000170.2 NP_000161.2	c.2T>C	p.Met1?	Founder variant in some Arab villages in Israel [Boneh et al 2005]
c.395C>T	p.Ser132Leu	Founder variant in New Zealand [Swanson et al 2015]
c.1166C>T	p.Ala398Val	Variant w/residual GCS activity [Swanson et al 2015]
NM_000170.2	c.2203-2A>G	--
NM_000170.2 NP_000161.2	c.2999delG	p.Cys1000LeufsTer31
c.1545G>C	p.Arg515Ser	Founder variant in the United Kingdom w/no GCS activity [Toone et al 2001]
c.1691G>T	p.Ser564Ile	Founder variant in Finland w/no residual activity [Kure et al 1992]
c.2284G>A	p.Gly761Arg	Founder variant in Finland w/no residual activity [Kure et al 1999, Coughlin et al 2017]
NM_000170.2	Del exons 1-8	--	Founder variant in Finland [Coughlin et al 2017]
NM_000170.2 NP_000161.2	c.1166C>T	p.Ala389Val	Common variants; have residual activity [Korman et al 2004, Kure et al 2004, Swanson et al 2015, Bravo-Alonso et al 2017]
c.1382G>A	p.Arg461Gln
c.2368C>T	p.Arg790Trp
c.2405C>T	p.Ala802Val
c.2714T>C	p.Val905Gly
c.2311G>A	p.Gly771Arg	Common variant [Coughlin et al 2017]
c.1009C>T	p.Arg337Ter	Common variants; no residual activity [Coughlin et al 2017]
c.1270C>T	p.Arg424Ter
c.499G>T	p.Glu167Ter
NM_000170.2	c.2316-1G>A (IVS19-1G>A)	--
c.2665+1G>C (IVS22+1G>C)	--
c.2919+1G>A (IVS24+1G>A)	--

Gene ¹

Reference Sequences

DNA Nucleotide Change
(Alias ²)

Predicted Protein Change

Comment [References]

AMT

NM_000481.2
NP_000472.2

c.317T>C

p.Ile106Thr

Founder variant in the Netherlands w/residual GCS activity [Swanson et al 2015]

c.2T>C

p.Met1?

Common variant; assumed no activity [Swanson et al 2015]

c.959G>A

p.Arg320His

Common variant w/no residual GCS activity [Coughlin et al 2017]

c.217C>T

p.Arg73Cys

Common variants [Coughlin et al 2017]

c.280C>T

p.Arg94Trp

NM_000481.2

c.471+2T>C

NM_000481.2
NP_000472.2

c.664C>T

p.Arg222Cys

NM_000481.2

c.878-1G>A

NM_000481.2
NP_000472.2

c.887G>A

p.Arg296His

c.921G>A

p.Val307Val

Common variant; creates new splice site [Coughlin et al 2017]

GLDC

NM_000170.2
NP_000161.2

c.2T>C

p.Met1?

Founder variant in some Arab villages in Israel [Boneh et al 2005]

c.395C>T

p.Ser132Leu

Founder variant in New Zealand [Swanson et al 2015]

c.1166C>T

p.Ala398Val

Variant w/residual GCS activity [Swanson et al 2015]

NM_000170.2

c.2203-2A>G

NM_000170.2
NP_000161.2

c.2999delG

p.Cys1000LeufsTer31

c.1545G>C

p.Arg515Ser

Founder variant in the United Kingdom w/no GCS activity [Toone et al 2001]

c.1691G>T

p.Ser564Ile

Founder variant in Finland w/no residual activity [Kure et al 1992]

c.2284G>A

p.Gly761Arg

Founder variant in Finland w/no residual activity [Kure et al 1999, Coughlin et al 2017]

NM_000170.2

Del exons 1-8

Founder variant in Finland [Coughlin et al 2017]

NM_000170.2
NP_000161.2

c.1166C>T

p.Ala389Val

Common variants; have residual activity [Korman et al 2004, Kure et al 2004, Swanson et al 2015, Bravo-Alonso et al 2017]

c.1382G>A

p.Arg461Gln

c.2368C>T

p.Arg790Trp

c.2405C>T

p.Ala802Val

c.2714T>C

p.Val905Gly

c.2311G>A

p.Gly771Arg

Common variant [Coughlin et al 2017]

c.1009C>T

p.Arg337Ter

Common variants; no residual activity [Coughlin et al 2017]

c.1270C>T

p.Arg424Ter

c.499G>T

p.Glu167Ter

NM_000170.2

c.2316-1G>A
(IVS19-1G>A)

c.2665+1G>C
(IVS22+1G>C)

c.2919+1G>A
(IVS24+1G>A)

From: Nonketotic Hyperglycinemia

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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