3-49419325-C-T

Position:

chr3-49419325-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000481.4(AMT):c.631G>A(p.Glu211Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,614,230 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 109 hom. )

Consequence

AMT
NM_000481.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 2.57

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:

ENSG00000283189 (HGNC:):

ENSG00000283189 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008803636).

BP6

Variant 3-49419325-C-T is Benign according to our data. Variant chr3-49419325-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 462898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49419325-C-T is described in Lovd as [Benign]. Variant chr3-49419325-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00791 (1205/152350) while in subpopulation SAS AF= 0.0174 (84/4832). AF 95% confidence interval is 0.0144. There are 5 homozygotes in gnomad4. There are 601 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMT	NM_000481.4 linkuse as main transcript	c.631G>A	p.Glu211Lys	missense_variant	6/9	ENST00000273588.9	NP_000472.2	P48728-1A0A024R2U7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMT	ENST00000273588.9 linkuse as main transcript	c.631G>A	p.Glu211Lys	missense_variant	6/9	1	NM_000481.4	ENSP00000273588.3		P48728-1
ENSG00000283189	ENST00000636166.1 linkuse as main transcript	c.868G>A	p.Glu290Lys	missense_variant	8/11	5		ENSP00000490106.1		A0A1B0GUH1

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1202

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00994

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.0105

AC:

2635

AN:

250992

Hom.:

AF XY:

0.0117

AC XY:

1586

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00581

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0191

Gnomad FIN exome

AF:

0.0121

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00888

AC:

12975

AN:

1461880

Hom.:

109

Cov.:

AF XY:

0.00949

AC XY:

6901

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00660

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0182

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.00825

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00791

AC:

1205

AN:

152350

Hom.:

Cov.:

AF XY:

0.00807

AC XY:

601

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0131

Gnomad4 NFE

AF:

0.00994

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00997

Hom.:

Bravo

AF:

0.00720

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.0109

AC:

1327

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0131

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycine encephalopathy

Benign:7

Likely benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	AMT: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 11, 2018	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;.;.;T;T;T;.;.;T;T;.;.

Eigen

Benign

0.092

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0088

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.19

N;N;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

N;N;N;.;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.44

Sift

Benign

0.66

T;T;T;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.80

T;T;T;.;.;.;.;.;.;.;.;.

Polyphen

0.019

B;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.18

MPC

0.23

ClinPred

0.0099

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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