Variant 3-49417897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000481.4(AMT):c.954G>A(p.Arg318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,826 control chromosomes in the GnomAD database, including 75,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6559 hom., cov: 31)

Exomes 𝑓: 0.30 ( 68709 hom. )

Consequence

AMT
NM_000481.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.891

Variant links:

Genes affected

AMT (HGNC:473): (aminomethyltransferase) This gene encodes one of four critical components of the glycine cleavage system. Mutations in this gene have been associated with glycine encephalopathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

AMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 3-49417897-C-T is Benign according to our data. Variant chr3-49417897-C-T is described in ClinVar as [Benign]. Clinvar id is 256240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49417897-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.891 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMT	NM_000481.4 linkuse as main transcript	c.954G>A	p.Arg318=	synonymous_variant	8/9	ENST00000273588.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMT	ENST00000273588.9 linkuse as main transcript	c.954G>A	p.Arg318=	synonymous_variant	8/9	1	NM_000481.4	P1	P48728-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42689

AN:

151924

Hom.:

6557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.0584

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.276

AC:

69306

AN:

251004

Hom.:

11201

AF XY:

0.280

AC XY:

38047

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.0558

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.298

AC:

435990

AN:

1461786

Hom.:

68709

Cov.:

AF XY:

0.297

AC XY:

216045

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.235

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.0630

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.281

AC:

42703

AN:

152040

Hom.:

6559

Cov.:

AF XY:

0.284

AC XY:

21086

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.0587

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.299

Hom.:

15254

Bravo

AF:

0.258

Asia WGS

AF:

0.143

AC:

503

AN:

3478

EpiCase

AF:

0.317

EpiControl

AF:

0.311

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Non-ketotic hyperglycinemia

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Nov 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 26, 2020	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 22, 2019	This variant is associated with the following publications: (PMID: 28502726, 12948742, 22171071) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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