chr6-42960779-C-A

Variant names:

• chr6-42960779-C-A
• NM_018960.6:c.12C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_018960.6(GNMT):​c.12C>A​(p.Ser4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,389,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GNMT NM_018960.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773

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]

CNPY3-GNMT (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity GNMT_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3977031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNMT	NM_018960.6	c.12C>A	p.Ser4Arg	missense_variant	Exon 1 of 6	ENST00000372808.4	NP_061833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4	c.12C>A	p.Ser4Arg	missense_variant	Exon 1 of 6	1	NM_018960.6	ENSP00000361894.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1389906 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 684644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000277

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.066
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.38
MutPred		0.29		Gain of MoRF binding (P = 0.0113);
MVP		0.60
MPC		1.7
ClinPred		0.91	D
GERP RS		0.81
Varity_R		0.30
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42928517;