12-57626799-G-A

Position:

chr12-57626799-G-A

Variant summary

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

The NM_001478.5(B4GALNT1):c.1547C>T(p.Ala516Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00961 in 1,614,208 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 86 hom. )

Consequence

B4GALNT1
NM_001478.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

B4GALNT1 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=0.003937304).

BP6

Variant 12-57626799-G-A is Benign according to our data. Variant chr12-57626799-G-A is described in ClinVar as [Benign]. Clinvar id is 235331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57626799-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00735 (1119/152322) while in subpopulation NFE AF= 0.0116 (788/68016). AF 95% confidence interval is 0.0109. There are 3 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALNT1	NM_001478.5 linkuse as main transcript	c.1547C>T	p.Ala516Val	missense_variant	11/11	ENST00000341156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALNT1	ENST00000341156.9 linkuse as main transcript	c.1547C>T	p.Ala516Val	missense_variant	11/11	1	NM_001478.5	P1	Q00973-1

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

1120

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00741

AC:

1864

AN:

251486

Hom.:

AF XY:

0.00734

AC XY:

998

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.00985

AC:

14401

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00971

AC XY:

7062

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.0154

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00866

GnomAD4 genome

AF:

0.00735

AC:

1119

AN:

152322

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00950

Hom.:

Bravo

AF:

0.00598

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00749

AC:

909

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.00818

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	B4GALNT1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 27, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.57

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.039

Sift

Benign

0.56

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.017

B;.

Vest4

0.062

MVP

0.22

MPC

0.91

ClinPred

0.0091

GERP RS

4.6

Varity_R

0.063

gMVP

0.36

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