Variant 7-71388395-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022479.3(GALNT17):c.583G>A(p.Asp195Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

GALNT17
NM_022479.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.91

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 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=0.4050405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT17	NM_022479.3 link	c.583G>A	p.Asp195Asn	missense_variant	3/11	ENST00000333538.10	NP_071924.1	Q6IS24Q2L4S5
GALNT17	XM_011516467.4 link	c.583G>A	p.Asp195Asn	missense_variant	3/10		XP_011514769.1
GALNT17	XM_017012521.3 link	c.583G>A	p.Asp195Asn	missense_variant	3/7		XP_016868010.1
GALNT17	XM_011516469.4 link	c.583G>A	p.Asp195Asn	missense_variant	3/6		XP_011514771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GALNT17	ENST00000333538.10 link	c.583G>A	p.Asp195Asn	missense_variant	3/11	1	NM_022479.3	ENSP00000329654.5	Q6IS24
GALNT17	ENST00000447516.5 link	c.517G>A	p.Asp173Asn	missense_variant	3/4	4		ENSP00000392019.1	H7BZX9
GALNT17	ENST00000467723.1 link	n.517G>A		non_coding_transcript_exon_variant	3/11	2
GALNT17	ENST00000498380.6 link	n.985G>A		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250650

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Sep 12, 2023

The c.583G>A (p.D195N) alteration is located in exon 3 (coding exon 3) of the WBSCR17 gene. This alteration results from a G to A substitution at nucleotide position 583, causing the aspartic acid (D) at amino acid position 195 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

T;.;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;D;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.28

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.21

T;T;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.33

B;.;.

Vest4

0.72

MutPred

0.47

Loss of phosphorylation at S194 (P = 0.1125);.;.;

MVP

0.70

MPC

1.5

ClinPred

0.64

GERP RS

5.6

Varity_R

0.091

gMVP

0.40

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