13-94155254-G-T

Variant names:

• chr13-94155254-G-T
• rs497836
• NM_005708.5:c.877+127360G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005708.5(GPC6):​c.877+127360G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,776 control chromosomes in the GnomAD database, including 27,025 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 0.58 (27025 hom., cov: 30)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 4 publications found

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]

GPC6-AS1 (HGNC:39909): (GPC6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005708.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.877+127360G>T		intron	N/A	NP_005699.1
	GPC6-AS1	NR_046535.1		n.485-848C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	ENST00000377047.9	TSL:1 MANE Select	c.877+127360G>T		intron	N/A	ENSP00000366246.3
	GPC6-AS1	ENST00000436329.2	TSL:5	n.485-848C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88136 AN: 151658 Hom.: 27023 Cov.: 30

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.581 AC: 88156 AN: 151776 Hom.: 27025 Cov.: 30 AF XY: 0.584 AC XY: 43341 AN XY: 74162

African (AFR) AF: 0.375 AC: 15488 AN: 41348

American (AMR) AF: 0.627 AC: 9538 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1963 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3287 AN: 5144

South Asian (SAS) AF: 0.574 AC: 2761 AN: 4808

European-Finnish (FIN) AF: 0.727 AC: 7654 AN: 10526

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45475 AN: 67950

Other (OTH) AF: 0.585 AC: 1231 AN: 2104

Alfa AF: 0.629 Hom.: 14208

Bravo AF: 0.566

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.48
DANN	Benign	0.75
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs497836; hg19: chr13-94807508;