7-71335610-C-T

Variant summary

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

The NM_022479.3(GALNT17):c.299C>T(p.Pro100Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,612,686 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.39

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=0.23138353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT17	NM_022479.3	c.299C>T	p.Pro100Leu	missense_variant	2/11	ENST00000333538.10
GALNT17	XM_011516467.4	c.299C>T	p.Pro100Leu	missense_variant	2/10
GALNT17	XM_017012521.3	c.299C>T	p.Pro100Leu	missense_variant	2/7
GALNT17	XM_011516469.4	c.299C>T	p.Pro100Leu	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT17	ENST00000333538.10	c.299C>T	p.Pro100Leu	missense_variant	2/11	1	NM_022479.3	P1
GALNT17	ENST00000447516.5	c.233C>T	p.Pro78Leu	missense_variant	2/4	4
GALNT17	ENST00000467723.1	n.233C>T		non_coding_transcript_exon_variant	2/11	2
GALNT17	ENST00000498380.6	n.701C>T		non_coding_transcript_exon_variant	2/11	2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000136 AC: 34 AN: 249412 Hom.: 0 AF XY: 0.000148 AC XY: 20 AN XY: 134934

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.0000587

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000188 AC: 274 AN: 1460446 Hom.: 1 Cov.: 31 AF XY: 0.000182 AC XY: 132 AN XY: 726500

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000673

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.000407

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000205

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74426

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000199 Hom.: 0

Bravo AF: 0.000128

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.000492

EpiControl AF: 0.000179

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

Jun 01, 2023

The c.299C>T (p.P100L) alteration is located in exon 2 (coding exon 2) of the WBSCR17 gene. This alteration results from a C to T substitution at nucleotide position 299, causing the proline (P) at amino acid position 100 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.55	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.017	D;T;D
Polyphen		0.78	P;.;.
Vest4		0.77
MVP		0.87
MPC		0.66
ClinPred		0.12	T
GERP RS		4.9
Varity_R		0.10
gMVP		0.75

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: rs140476927; hg19: chr7-70800596; COSMIC: COSV61145711;