13-93226778-A-G

Variant names:

• chr13-93226778-A-G
• rs7985891
• XM_047429990.1:c.-51+96A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_047429990.1(GPC6):​c.-51+96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 152,140 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (149 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: GPC6 XM_047429990.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.691

Genes affected

GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]

ENSG00000278177 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 13-93226778-A-G is Benign according to our data. Variant chr13-93226778-A-G is described in ClinVar as [Benign]. Clinvar id is 1257500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	XM_047429990.1	c.-51+96A>G		intron_variant	Intron 1 of 8		XP_047285946.1
GPC6	NM_005708.5	c.-679A>G		upstream_gene_variant		ENST00000377047.9	NP_005699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000278177	ENST00000610286.1	n.540T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
GPC6	ENST00000377047.9	c.-679A>G		upstream_gene_variant		1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5601 AN: 151928 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0106 AC: 1 AN: 94 Hom.: 0 Cov.: 0 AF XY: 0.0179 AC XY: 1 AN XY: 56

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0369 AC: 5604 AN: 152046 Hom.: 149 Cov.: 32 AF XY: 0.0376 AC XY: 2794 AN XY: 74344

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.00913

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0310 Hom.: 35

Bravo AF: 0.0390

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.53
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7985891; hg19: chr13-93879031;