Variant rs4987174 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+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0627 in 1,613,276 control chromosomes in the GnomAD database, including 4,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 1205 hom., cov: 31)

Exomes 𝑓: 0.059 ( 3164 hom. )

Consequence

GNMT
NM_018960.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80

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=-0.92).

BP6

Variant 6-42963477-C-T is Benign according to our data. Variant chr6-42963477-C-T is described in ClinVar as [Benign]. Clinvar id is 1288001.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNMT	NM_018960.6 linkuse as main transcript	c.716+28C>T		intron_variant		ENST00000372808.4
CNPY3-GNMT	NR_134890.2 linkuse as main transcript	n.578+28C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNMT	ENST00000372808.4 linkuse as main transcript	c.716+28C>T		intron_variant		1	NM_018960.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

14965

AN:

151828

Hom.:

1200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0419

Gnomad AMR

AF:

0.0583

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.0556

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0540

Gnomad OTH

AF:

0.0882

GnomAD3 exomes

AF:

0.0625

AC:

15712

AN:

251310

Hom.:

761

AF XY:

0.0603

AC XY:

8192

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.0413

Gnomad ASJ exome

AF:

0.0457

Gnomad EAS exome

AF:

0.0671

Gnomad SAS exome

AF:

0.0610

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0590

AC:

86157

AN:

1461332

Hom.:

3164

Cov.:

AF XY:

0.0586

AC XY:

42586

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.0437

Gnomad4 ASJ exome

AF:

0.0450

Gnomad4 EAS exome

AF:

0.0642

Gnomad4 SAS exome

AF:

0.0615

Gnomad4 FIN exome

AF:

0.0351

Gnomad4 NFE exome

AF:

0.0553

Gnomad4 OTH exome

AF:

0.0671

GnomAD4 genome

AF:

0.0987

AC:

14999

AN:

151944

Hom.:

1205

Cov.:

AF XY:

0.0954

AC XY:

7084

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.0556

Gnomad4 SAS

AF:

0.0592

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0540

Gnomad4 OTH

AF:

0.0878

Alfa

AF:

0.0716

Hom.:

133

Bravo

AF:

0.107

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

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 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

DANN

Benign

0.50

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

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