Genetic Variant GALNT17:p.Pro212Ser (chr7-71415933-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022479.3(GALNT17):c.634C>T(p.Pro212Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GALNT17
NM_022479.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT17	NM_022479.3 link	c.634C>T	p.Pro212Ser	missense_variant	Exon 4 of 11	ENST00000333538.10	NP_071924.1	Q6IS24Q2L4S5
GALNT17	XM_011516467.4 link	c.634C>T	p.Pro212Ser	missense_variant	Exon 4 of 10		XP_011514769.1
GALNT17	XM_017012521.3 link	c.634C>T	p.Pro212Ser	missense_variant	Exon 4 of 7		XP_016868010.1
GALNT17	XM_011516469.4 link	c.634C>T	p.Pro212Ser	missense_variant	Exon 4 of 6		XP_011514771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT17	ENST00000333538.10 link	c.634C>T	p.Pro212Ser	missense_variant	Exon 4 of 11	1	NM_022479.3	ENSP00000329654.5	Q6IS24
GALNT17	ENST00000467723.1 link	n.568C>T		non_coding_transcript_exon_variant	Exon 4 of 11	2
GALNT17	ENST00000498380.6 link	n.1036C>T		non_coding_transcript_exon_variant	Exon 4 of 11	2
GALNT17	ENST00000447516.5 link	c.*2C>T		downstream_gene_variant		4		ENSP00000392019.1	H7BZX9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250088

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461064

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.634C>T (p.P212S) alteration is located in exon 4 (coding exon 4) of the WBSCR17 gene. This alteration results from a C to T substitution at nucleotide position 634, causing the proline (P) at amino acid position 212 to be replaced by a serine (S). 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

0.61

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.096

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

-0.14

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-7.2

D;.

REVEL

Uncertain

0.49

Sift

Benign

0.034

D;.

Sift4G

Benign

0.091

T;T

Polyphen

1.0

D;.

Vest4

0.79

MutPred

0.45

Gain of MoRF binding (P = 0.0475);.;

MVP

0.89

MPC

1.3

ClinPred

0.79

GERP RS

5.2

Varity_R

0.44

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over