Variant rs2296805 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.206+47T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,456,542 control chromosomes in the GnomAD database, including 264,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.66 ( 35321 hom., cov: 33)

Exomes 𝑓: 0.59 ( 229499 hom. )

Consequence

GNMT
NM_018960.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.96

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=-0.81).

BP6

Variant 6-42961020-T-G is Benign according to our data. Variant chr6-42961020-T-G is described in ClinVar as [Benign]. Clinvar id is 1265698.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 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.206+47T>G		intron_variant		ENST00000372808.4
CNPY3-GNMT	NR_134890.2 linkuse as main transcript	n.340-1742T>G		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.206+47T>G		intron_variant		1	NM_018960.6	P1

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100590

AN:

152078

Hom.:

35265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.646

GnomAD3 exomes

AF:

0.574

AC:

67666

AN:

117892

Hom.:

20226

AF XY:

0.578

AC XY:

37381

AN XY:

64620

show subpopulations

Gnomad AFR exome

AF:

0.924

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.649

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.589

AC:

767795

AN:

1304346

Hom.:

229499

Cov.:

AF XY:

0.590

AC XY:

379411

AN XY:

642802

show subpopulations

Gnomad4 AFR exome

AF:

0.925

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.515

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.507

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.662

AC:

100709

AN:

152196

Hom.:

35321

Cov.:

AF XY:

0.655

AC XY:

48733

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.911

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.523

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.648

Alfa

AF:

0.597

Hom.:

8011

Bravo

AF:

0.677

Asia WGS

AF:

0.544

AC:

1895

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

-0.81

CADD

Benign

8.5

DANN

Benign

0.56

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