chr2-165748856-A-G

Position:

chr2-165748856-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004482.4(GALNT3):c.1827T>C(p.Asn609=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00952 in 1,611,598 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 88 hom. )

Consequence

GALNT3
NM_004482.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

GALNT3 (HGNC:4125): (polypeptide N-acetylgalactosaminyltransferase 3) This gene encodes UDP-GalNAc transferase 3, a member of the GalNAc-transferases family. This family transfers an N-acetyl galactosamine to the hydroxyl group of a serine or threonine residue in the first step of O-linked oligosaccharide biosynthesis. Individual GalNAc-transferases have distinct activities and initiation of O-glycosylation is regulated by a repertoire of GalNAc-transferases. The protein encoded by this gene is highly homologous to other family members, however the enzymes have different substrate specificities. [provided by RefSeq, Jul 2008]

GALNT3 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=-0.5).

BP6

Variant 2-165748856-A-G is Benign according to our data. Variant chr2-165748856-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 773430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00757 (1153/152214) while in subpopulation NFE AF= 0.0124 (844/67966). AF 95% confidence interval is 0.0117. There are 9 homozygotes in gnomad4. There are 524 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALNT3	NM_004482.4 linkuse as main transcript	c.1827T>C	p.Asn609=	synonymous_variant	11/11	ENST00000392701.8
GALNT3	XM_005246449.2 linkuse as main transcript	c.1827T>C	p.Asn609=	synonymous_variant	11/11
GALNT3	XM_011510929.2 linkuse as main transcript	c.1827T>C	p.Asn609=	synonymous_variant	11/11
GALNT3	XM_017003770.2 linkuse as main transcript	c.1827T>C	p.Asn609=	synonymous_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT3	ENST00000392701.8 linkuse as main transcript	c.1827T>C	p.Asn609=	synonymous_variant	11/11	1	NM_004482.4	P1	Q14435-1
GALNT3	ENST00000409882.5 linkuse as main transcript	c.1041T>C	p.Asn347=	synonymous_variant	8/8	1

Frequencies

GnomAD3 genomes

AF:

0.00758

AC:

1153

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00797

AC:

1973

AN:

247604

Hom.:

AF XY:

0.00804

AC XY:

1077

AN XY:

134006

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00540

Gnomad ASJ exome

AF:

0.0253

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00243

Gnomad FIN exome

AF:

0.00274

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00972

AC:

14186

AN:

1459384

Hom.:

Cov.:

AF XY:

0.00958

AC XY:

6952

AN XY:

726012

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00609

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00281

Gnomad4 FIN exome

AF:

0.00272

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.00757

AC:

1153

AN:

152214

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

524

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00707

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00770

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.0134

EpiControl

AF:

0.0127

ClinVar

Significance: Benign/Likely 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Tumoral calcinosis, hyperphosphatemic, familial, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

GALNT3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 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

-0.50

CADD

Benign

7.3

DANN

Benign

0.68

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