22-42692965-C-T

Position:

chr22-42692965-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017436.7(A4GALT):c.987G>A(p.Thr329=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,612,248 control chromosomes in the GnomAD database, including 107,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11655 hom., cov: 33)

Exomes 𝑓: 0.36 ( 95863 hom. )

Consequence

A4GALT
NM_017436.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.745

Variant links:

Genes affected

A4GALT (HGNC:18149): (alpha 1,4-galactosyltransferase (P1PK blood group)) The protein encoded by this gene catalyzes the transfer of galactose to lactosylceramide to form globotriaosylceramide, which has been identified as the P(k) antigen of the P blood group system. This protein, a type II membrane protein found in the Golgi, is also required for the synthesis of the bacterial verotoxins receptor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

A4GALT links:

CYB5R3 (HGNC:2873): (cytochrome b5 reductase 3) This gene encodes cytochrome b5 reductase, which includes a membrane-bound form in somatic cells (anchored in the endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The membrane-bound form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound form has both membrane-binding and catalytic domains, while the soluble form has only the catalytic domain. Alternate splicing results in multiple transcript variants. Mutations in this gene cause methemoglobinemias. [provided by RefSeq, Jan 2010]

CYB5R3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 22-42692965-C-T is Benign according to our data. Variant chr22-42692965-C-T is described in ClinVar as [Benign]. Clinvar id is 1600484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.745 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A4GALT	NM_017436.7 linkuse as main transcript	c.987G>A	p.Thr329=	synonymous_variant	3/3	ENST00000642412.2	NP_059132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A4GALT	ENST00000642412.2 linkuse as main transcript	c.987G>A	p.Thr329=	synonymous_variant	3/3		NM_017436.7	ENSP00000494127	P1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58383

AN:

151938

Hom.:

11658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.350

AC:

87481

AN:

249724

Hom.:

16091

AF XY:

0.348

AC XY:

47085

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.373

GnomAD4 exome

AF:

0.358

AC:

523029

AN:

1460192

Hom.:

95863

Cov.:

AF XY:

0.356

AC XY:

258576

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.483

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.384

AC:

58395

AN:

152056

Hom.:

11655

Cov.:

AF XY:

0.379

AC XY:

28148

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.481

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.379

Hom.:

16539

Bravo

AF:

0.393

Asia WGS

AF:

0.264

AC:

920

AN:

3478

EpiCase

AF:

0.364

EpiControl

AF:

0.380

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

A4GALT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.0

DANN

Benign

0.58

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