Variant rs4987173 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018960.6(GNMT):c.716+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,324 control chromosomes in the GnomAD database, including 152,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13022 hom., cov: 31)

Exomes 𝑓: 0.43 ( 139946 hom. )

Consequence

GNMT
NM_018960.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.491

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:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-42963486-G-A is Benign according to our data. Variant chr6-42963486-G-A is described in ClinVar as [Benign]. Clinvar id is 1251337.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNMT	NM_018960.6 linkuse as main transcript	c.716+37G>A		intron_variant		ENST00000372808.4	NP_061833.1
CNPY3-GNMT	NR_134890.2 linkuse as main transcript	n.578+37G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNMT	ENST00000372808.4 linkuse as main transcript	c.716+37G>A		intron_variant		1	NM_018960.6	ENSP00000361894	P1

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62049

AN:

151830

Hom.:

13017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.421

GnomAD3 exomes

AF:

0.386

AC:

96861

AN:

251258

Hom.:

20158

AF XY:

0.396

AC XY:

53829

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.401

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.432

AC:

631602

AN:

1461380

Hom.:

139946

Cov.:

AF XY:

0.434

AC XY:

315404

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.401

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.433

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.453

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.409

AC:

62090

AN:

151944

Hom.:

13022

Cov.:

AF XY:

0.404

AC XY:

30014

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.395

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.434

Hom.:

3127

Bravo

AF:

0.401

Asia WGS

AF:

0.258

AC:

899

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.57

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over