7-71415948-G-A

Variant names:

• chr7-71415948-G-A
• rs765586512
• NM_022479.3:c.649G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022479.3(GALNT17):​c.649G>A​(p.Val217Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT17	NM_022479.3	c.649G>A	p.Val217Met	missense_variant	Exon 4 of 11	ENST00000333538.10	NP_071924.1
GALNT17	XM_011516467.4	c.649G>A	p.Val217Met	missense_variant	Exon 4 of 10		XP_011514769.1
GALNT17	XM_017012521.3	c.649G>A	p.Val217Met	missense_variant	Exon 4 of 7		XP_016868010.1
GALNT17	XM_011516469.4	c.649G>A	p.Val217Met	missense_variant	Exon 4 of 6		XP_011514771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT17	ENST00000333538.10	c.649G>A	p.Val217Met	missense_variant	Exon 4 of 11	1	NM_022479.3	ENSP00000329654.5
GALNT17	ENST00000467723.1	n.583G>A		non_coding_transcript_exon_variant	Exon 4 of 11	2
GALNT17	ENST00000498380.6	n.1051G>A		non_coding_transcript_exon_variant	Exon 4 of 11	2
GALNT17	ENST00000447516.5	c.*17G>A		downstream_gene_variant		4		ENSP00000392019.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.649G>A (p.V217M) alteration is located in exon 4 (coding exon 4) of the WBSCR17 gene. This alteration results from a G to A substitution at nucleotide position 649, causing the valine (V) at amino acid position 217 to be replaced by a methionine (M). 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	0.36
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	-0.13	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.28
Sift	Benign	0.073	T;.
Sift4G	Uncertain	0.051	T;D
Polyphen		0.57	P;.
Vest4		0.74
MutPred		0.63		Loss of methylation at K216 (P = 0.0177);.;
MVP		0.72
MPC		0.98
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.14
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs765586512; hg19: chr7-70880934;