NM_018960.6:c.41C>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018960.6(GNMT):c.41C>G(p.Ala14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,554,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

GNMT
NM_018960.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Publications

0 publications found

Variant links:

Genes affected

GNMT (HGNC:4415): (glycine N-methyltransferase) The protein encoded by this gene is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine (along with glycine) to S-adenosyl-L-homocysteine and sarcosine. This protein is found in the cytoplasm and acts as a homotetramer. Defects in this gene are a cause of GNMT deficiency (hypermethioninemia). Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between the upstream CNPY3 (canopy FGF signaling regulator 3) gene and this gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

GNMT links:

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PEX6 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 4A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health
peroxisome biogenesis disorder 4B
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Heimler syndrome 2
Inheritance: AR Classification: MODERATE Submitted by: G2P
autosomal recessive cerebellar ataxia-blindness-deafness syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX6 links:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17275488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018960.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNMT	NM_018960.6	MANE Select	c.41C>G	p.Ala14Gly	missense	Exon 1 of 6	NP_061833.1	Q14749
GNMT	NM_001318865.2		c.41C>G	p.Ala14Gly	missense	Exon 1 of 6	NP_001305794.1	A0A0S2Z5F2
CNPY3-GNMT	NM_001318857.2		c.152-1954C>G		intron	N/A	NP_001305786.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNMT	ENST00000372808.4	TSL:1 MANE Select	c.41C>G	p.Ala14Gly	missense	Exon 1 of 6	ENSP00000361894.3	Q14749
GNMT	ENST00000858688.1		c.41C>G	p.Ala14Gly	missense	Exon 1 of 6	ENSP00000528747.1
GNMT	ENST00000858686.1		c.41C>G	p.Ala14Gly	missense	Exon 1 of 6	ENSP00000528745.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000635

AC:

AN:

157400

AF XY:

0.0000117

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000499

AC:

AN:

1401970

Hom.:

Cov.:

AF XY:

0.00000433

AC XY:

AN XY:

692184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31994

American (AMR)

AF:

0.00

AC:

AN:

36982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25032

East Asian (EAS)

AF:

0.00

AC:

AN:

36544

South Asian (SAS)

AF:

0.00

AC:

AN:

79782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.00000646

AC:

AN:

1083632

Other (OTH)

AF:

0.00

AC:

AN:

58132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.54

PhyloP100

1.8

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.88

REVEL

Benign

0.15

Sift

Benign

0.27

Sift4G

Benign

0.44

Polyphen

0.045

Vest4

0.25

MutPred

0.32

Gain of catalytic residue at A14 (P = 0.0643)

MVP

0.42

MPC

1.1

ClinPred

0.23

GERP RS

4.0

PromoterAI

-0.055

Neutral

(source)

Varity_R

0.19

gMVP

0.72

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over