Variant 2-165748813-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_004482.4(GALNT3):c.1870C>T(p.Leu624Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,611,626 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

GALNT3
NM_004482.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.62

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011095703).

BP6

Variant 2-165748813-G-A is Benign according to our data. Variant chr2-165748813-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715285.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000124 (181/1459584) while in subpopulation AMR AF= 0.00395 (176/44510). AF 95% confidence interval is 0.00348. There are 1 homozygotes in gnomad4_exome. There are 75 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALNT3	NM_004482.4 linkuse as main transcript	c.1870C>T	p.Leu624Phe	missense_variant	11/11	ENST00000392701.8
GALNT3	XM_005246449.2 linkuse as main transcript	c.1870C>T	p.Leu624Phe	missense_variant	11/11
GALNT3	XM_011510929.2 linkuse as main transcript	c.1870C>T	p.Leu624Phe	missense_variant	11/11
GALNT3	XM_017003770.2 linkuse as main transcript	c.1870C>T	p.Leu624Phe	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT3	ENST00000392701.8 linkuse as main transcript	c.1870C>T	p.Leu624Phe	missense_variant	11/11	1	NM_004482.4	P1	Q14435-1
GALNT3	ENST00000409882.5 linkuse as main transcript	c.1084C>T	p.Leu362Phe	missense_variant	8/8	1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000679

AC:

169

AN:

248852

Hom.:

AF XY:

0.000490

AC XY:

AN XY:

134652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000124

AC:

181

AN:

1459584

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

726142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00395

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000112

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.000287

ExAC

AF:

0.000503

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;.

MutationTaster

Benign

0.75

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

1.3

N;N

REVEL

Benign

0.049

Sift

Benign

0.76

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;.

Vest4

0.055

MutPred

0.27

Loss of ubiquitination at K626 (P = 0.073);.;

MVP

0.33

MPC

0.097

ClinPred

0.052

GERP RS

3.8

Varity_R

0.10

gMVP

0.35

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