Variant rs7760250 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.207-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,237,874 control chromosomes in the GnomAD database, including 174,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 24780 hom., cov: 31)

Exomes 𝑓: 0.52 ( 149326 hom. )

Consequence

GNMT
NM_018960.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0140

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=-0.83).

BP6

Variant 6-42962101-G-A is Benign according to our data. Variant chr6-42962101-G-A is described in ClinVar as [Benign]. Clinvar id is 1230082.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 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.207-111G>A		intron_variant		ENST00000372808.4	NP_061833.1
CNPY3-GNMT	NR_134890.2 linkuse as main transcript	n.340-661G>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.207-111G>A		intron_variant		1	NM_018960.6	ENSP00000361894	P1

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84535

AN:

151790

Hom.:

24743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.727

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.550

GnomAD4 exome

AF:

0.516

AC:

560608

AN:

1085966

Hom.:

149326

AF XY:

0.518

AC XY:

287254

AN XY:

554710

show subpopulations

Gnomad4 AFR exome

AF:

0.730

Gnomad4 AMR exome

AF:

0.334

Gnomad4 ASJ exome

AF:

0.466

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.514

GnomAD4 genome

AF:

0.557

AC:

84624

AN:

151908

Hom.:

24780

Cov.:

AF XY:

0.548

AC XY:

40692

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.727

Gnomad4 AMR

AF:

0.418

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.491

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.546

Alfa

AF:

0.553

Hom.:

2964

Bravo

AF:

0.561

Asia WGS

AF:

0.352

AC:

1228

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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

DANN

Benign

0.67

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