dbSNP rs2271077: GALNT15:p.His510Tyr (chr3-16219913-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_054110.5(GALNT15):c.1528C>T(p.His510Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,612,530 control chromosomes in the GnomAD database, including 6,652 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.091 ( 791 hom., cov: 33)

Exomes 𝑓: 0.074 ( 5861 hom. )

Consequence

GALNT15
NM_054110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Variant links:

Genes affected

GALNT15 (HGNC:21531): (polypeptide N-acetylgalactosaminyltransferase 15) Predicted to enable polypeptide N-acetylgalactosaminyltransferase activity. Predicted to be involved in O-glycan processing. Located in transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

GALNT15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020534694).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT15	NM_054110.5 link	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10	ENST00000339732.10	NP_473451.3	Q8N3T1
GALNT15	NM_001319051.2 link	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10		NP_001305980.1	C9JGI4
GALNT15	NM_001319052.2 link	c.118C>T	p.His40Tyr	missense_variant	Exon 3 of 5		NP_001305981.1	Q4G146
GALNT15	XM_005264852.6 link	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10		XP_005264909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT15	ENST00000339732.10 link	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10	1	NM_054110.5	ENSP00000344260.5	Q8N3T1
GALNT15	ENST00000437509.3 link	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10	1		ENSP00000395873.1	C9JGI4
GALNT15	ENST00000489467.1 link	n.202C>T		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.0906

AC:

13789

AN:

152120

Hom.:

794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0660

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.0975

AC:

24508

AN:

251270

Hom.:

1764

AF XY:

0.104

AC XY:

14106

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.0578

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0961

GnomAD4 exome

AF:

0.0735

AC:

107403

AN:

1460292

Hom.:

5861

Cov.:

AF XY:

0.0787

AC XY:

57147

AN XY:

726570

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0512

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.0630

Gnomad4 NFE exome

AF:

0.0545

Gnomad4 OTH exome

AF:

0.0920

GnomAD4 genome

AF:

0.0906

AC:

13797

AN:

152238

Hom.:

791

Cov.:

AF XY:

0.0940

AC XY:

6999

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0659

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.0598

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0738

Hom.:

1263

Bravo

AF:

0.0903

TwinsUK

AF:

0.0523

AC:

194

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.124

AC:

546

ESP6500EA

AF:

0.0590

AC:

507

ExAC

AF:

0.100

AC:

12165

Asia WGS

AF:

0.175

AC:

606

AN:

3478

EpiCase

AF:

0.0682

EpiControl

AF:

0.0699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.073

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.93

L;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.026

Sift

Benign

0.21

T;T;.

Sift4G

Benign

0.92

T;T;T

Polyphen

0.010

B;.;.

Vest4

0.078

MPC

0.045

ClinPred

0.0082

GERP RS

4.5

Varity_R

0.16

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over