7-71388338-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022479.3(GALNT17):c.526G>A(p.Val176Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000724 in 1,613,916 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00054 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (1 hom.)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.18

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059221983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT17	NM_022479.3	c.526G>A	p.Val176Ile	missense_variant	3/11	ENST00000333538.10
GALNT17	XM_011516467.4	c.526G>A	p.Val176Ile	missense_variant	3/10
GALNT17	XM_017012521.3	c.526G>A	p.Val176Ile	missense_variant	3/7
GALNT17	XM_011516469.4	c.526G>A	p.Val176Ile	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT17	ENST00000333538.10	c.526G>A	p.Val176Ile	missense_variant	3/11	1	NM_022479.3	P1
GALNT17	ENST00000447516.5	c.460G>A	p.Val154Ile	missense_variant	3/4	4
GALNT17	ENST00000467723.1	n.460G>A		non_coding_transcript_exon_variant	3/11	2
GALNT17	ENST00000498380.6	n.928G>A		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes AF: 0.000540 AC: 82 AN: 151966 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000510 AC: 128 AN: 251184 Hom.: 0 AF XY: 0.000471 AC XY: 64 AN XY: 135740

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000942

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000744 AC: 1087 AN: 1461832 Hom.: 1 Cov.: 30 AF XY: 0.000694 AC XY: 505 AN XY: 727220

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000917

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.000539 AC: 82 AN: 152084 Hom.: 1 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74330

Gnomad4 AFR AF: 0.000338

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000753 Hom.: 0

Bravo AF: 0.000536

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000511 AC: 62

EpiCase AF: 0.000600

EpiControl AF: 0.000593

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

Jan 07, 2022

The c.526G>A (p.V176I) 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 526, causing the valine (V) at amino acid position 176 to be replaced by an isoleucine (I). 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	0.096
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	24
Dann	Benign	0.97
DEOGEN2	Benign	0.032	T;.;.
Eigen	Benign	0.057
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T;T;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.33	N;N;.
REVEL	Benign	0.22
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.72	P;.;.
Vest4		0.40
MVP		0.32
MPC		0.97
ClinPred		0.041	T
GERP RS		5.6
Varity_R		0.089
gMVP		0.31

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: rs145445110; hg19: chr7-70853324; COSMIC: COSV61164479;