7-71710800-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022479.3(GALNT17):c.1540G>A(p.Ala514Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16483697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT17	NM_022479.3	c.1540G>A	p.Ala514Thr	missense_variant	10/11	ENST00000333538.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT17	ENST00000333538.10	c.1540G>A	p.Ala514Thr	missense_variant	10/11	1	NM_022479.3	P1
GALNT17	ENST00000467723.1	n.1474G>A		non_coding_transcript_exon_variant	10/11	2
GALNT17	ENST00000498380.6	n.1942G>A		non_coding_transcript_exon_variant	10/11	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

Feb 16, 2023

The c.1540G>A (p.A514T) alteration is located in exon 10 (coding exon 10) of the WBSCR17 gene. This alteration results from a G to A substitution at nucleotide position 1540, causing the alanine (A) at amino acid position 514 to be replaced by a threonine (T). 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	0.098
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	23
Dann	Uncertain	0.98
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.39	N;.
REVEL	Benign	0.048
Sift	Benign	0.32	T;.
Sift4G	Benign	0.59	T;T
Polyphen		0.0	B;.
Vest4		0.42
MutPred		0.48		Gain of sheet (P = 0.0827);.;
MVP		0.54
MPC		0.59
ClinPred		0.65	D
GERP RS		5.2
Varity_R		0.043
gMVP		0.61

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

Other links and lift over

dbSNP: rs1320885111; hg19: chr7-71175785;