Variant 7-71335592-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022479.3(GALNT17):c.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,610,540 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: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

GALNT17
NM_022479.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

Variant links:

Genes affected

GALNT17 (HGNC:16347): (polypeptide N-acetylgalactosaminyltransferase 17) This gene encodes an N-acetylgalactosaminyltransferase. This gene is located centromeric to the common deleted region in Williams-Beuren syndrome (WBS), a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. This protein may play a role in membrane trafficking. [provided by RefSeq, Jan 2013]

GALNT17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039128035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALNT17	NM_022479.3 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	2/11	ENST00000333538.10
GALNT17	XM_011516467.4 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	2/10
GALNT17	XM_017012521.3 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	2/7
GALNT17	XM_011516469.4 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GALNT17	ENST00000333538.10 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	2/11	1	NM_022479.3	P1
GALNT17	ENST00000447516.5 linkuse as main transcript	c.215G>A	p.Arg72Gln	missense_variant	2/4	4
GALNT17	ENST00000467723.1 linkuse as main transcript	n.215G>A		non_coding_transcript_exon_variant	2/11	2
GALNT17	ENST00000498380.6 linkuse as main transcript	n.683G>A		non_coding_transcript_exon_variant	2/11	2

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000405

AC:

100

AN:

247028

Hom.:

AF XY:

0.000359

AC XY:

AN XY:

133772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00303

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.000525

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000455

AC:

663

AN:

1458442

Hom.:

Cov.:

AF XY:

0.000455

AC XY:

330

AN XY:

725492

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00342

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.000413

Gnomad4 NFE exome

AF:

0.000474

Gnomad4 OTH exome

AF:

0.000382

GnomAD4 genome

AF:

0.000401

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000620

Hom.:

Bravo

AF:

0.000423

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000338

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.281G>A (p.R94Q) alteration is located in exon 2 (coding exon 2) of the WBSCR17 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a glutamine (Q). 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

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.25

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.025

T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.010

N;N;.

REVEL

Benign

0.18

Sift

Benign

0.35

T;T;.

Sift4G

Benign

0.36

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.62

MVP

0.85

MPC

1.7

ClinPred

0.47

GERP RS

4.9

Varity_R

0.19

gMVP

0.63

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