7-71388309-C-T

Variant summary

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

The NM_022479.3(GALNT17):c.497C>T(p.Ser166Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT17	NM_022479.3	c.497C>T	p.Ser166Leu	missense_variant	3/11	ENST00000333538.10
GALNT17	XM_011516467.4	c.497C>T	p.Ser166Leu	missense_variant	3/10
GALNT17	XM_017012521.3	c.497C>T	p.Ser166Leu	missense_variant	3/7
GALNT17	XM_011516469.4	c.497C>T	p.Ser166Leu	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT17	ENST00000333538.10	c.497C>T	p.Ser166Leu	missense_variant	3/11	1	NM_022479.3	P1
GALNT17	ENST00000447516.5	c.431C>T	p.Ser144Leu	missense_variant	3/4	4
GALNT17	ENST00000467723.1	n.431C>T		non_coding_transcript_exon_variant	3/11	2
GALNT17	ENST00000498380.6	n.899C>T		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Oct 02, 2023

The c.497C>T (p.S166L) alteration is located in exon 3 (coding exon 3) of the WBSCR17 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the serine (S) at amino acid position 166 to be replaced by a leucine (L). 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	0.92
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
Cadd	Pathogenic	34
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.38	T;.;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.29	D
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.6	D;D;.
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.93
MutPred		0.81		Loss of catalytic residue at S166 (P = 0.3018);.;.;
MVP		0.89
MPC		0.98
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.87
gMVP		0.83

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: chr7-70853295; COSMIC: COSV61157415;