Variant 2-165748797-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004482.4(GALNT3):c.1886T>G(p.Leu629Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GALNT3
NM_004482.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.31

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32313335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4 link	c.1886T>G	p.Leu629Arg	missense_variant	Exon 11 of 11	ENST00000392701.8	NP_004473.2	Q14435-1
GALNT3	XM_005246449.2 link	c.1886T>G	p.Leu629Arg	missense_variant	Exon 11 of 11		XP_005246506.1	Q14435-1
GALNT3	XM_011510929.2 link	c.1886T>G	p.Leu629Arg	missense_variant	Exon 11 of 11		XP_011509231.1	Q14435-1
GALNT3	XM_017003770.2 link	c.1886T>G	p.Leu629Arg	missense_variant	Exon 11 of 11		XP_016859259.1	Q14435-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT3	ENST00000392701.8 link	c.1886T>G	p.Leu629Arg	missense_variant	Exon 11 of 11	1	NM_004482.4	ENSP00000376465.3		Q14435-1
GALNT3	ENST00000409882.5 link	c.1100T>G	p.Leu367Arg	missense_variant	Exon 8 of 8	1		ENSP00000386955.1		E7EUL0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248716

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jul 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1886T>G (p.L629R) alteration is located in exon 11 (coding exon 10) of the GALNT3 gene. This alteration results from a T to G substitution at nucleotide position 1886, causing the leucine (L) at amino acid position 629 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.

Eigen

Benign

0.095

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.4

N;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.048

B;.

Vest4

0.45

MutPred

0.61

Gain of MoRF binding (P = 9e-04);.;

MVP

0.81

MPC

0.13

ClinPred

0.67

GERP RS

5.9

Varity_R

0.88

gMVP

0.78

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