7-71665456-G-A

Position:

• chr7-71665456-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022479.3(GALNT17):​c.1126G>A​(p.Val376Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.95

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT17	NM_022479.3	c.1126G>A	p.Val376Met	missense_variant	7/11	ENST00000333538.10	NP_071924.1
GALNT17	XM_011516467.4	c.1126G>A	p.Val376Met	missense_variant	7/10		XP_011514769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT17	ENST00000333538.10	c.1126G>A	p.Val376Met	missense_variant	7/11	1	NM_022479.3	ENSP00000329654.5
GALNT17	ENST00000467723.1	n.1060G>A		non_coding_transcript_exon_variant	7/11	2
GALNT17	ENST00000498380.6	n.1528G>A		non_coding_transcript_exon_variant	7/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.1126G>A (p.V376M) alteration is located in exon 7 (coding exon 7) of the WBSCR17 gene. This alteration results from a G to A substitution at nucleotide position 1126, causing the valine (V) at amino acid position 376 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.41	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.0	N;.
REVEL	Uncertain	0.59
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.86		Loss of sheet (P = 0.0817);.;
MVP		0.76
MPC		1.0
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.36
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-71130441;