chr13-93293605-A-T

Position:

• chr13-93293605-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005708.5(GPC6):​c.160+65989A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,246 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.015 (24 hom., cov: 33)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0153 (2324/152246) while in subpopulation NFE AF= 0.0215 (1463/68012). AF 95% confidence interval is 0.0206. There are 24 homozygotes in gnomad4. There are 1194 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC6	NM_005708.5	c.160+65989A>T		intron_variant		ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-51+66923A>T		intron_variant			XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.160+65989A>T		intron_variant		1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2324 AN: 152128 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0153 AC: 2324 AN: 152246 Hom.: 24 Cov.: 33 AF XY: 0.0160 AC XY: 1194 AN XY: 74432

Gnomad4 AFR AF: 0.00361

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0182 Hom.: 2

Bravo AF: 0.0128

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.44

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: rs143258881; hg19: chr13-93945858;