rs9556365

Variant names:

• chr13-94364984-T-G
• rs9556365
• NM_005708.5:c.1153-17430T>G

Variant summary

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

The NM_005708.5(GPC6):​c.1153-17430T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,166 control chromosomes in the GnomAD database, including 3,911 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 0.21 (3911 hom., cov: 33)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 9 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 Gene-Disease associations (from GenCC):

• autosomal recessive omodysplasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.1153-17430T>G		intron_variant	Intron 6 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.943-17430T>G		intron_variant	Intron 6 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.943-17430T>G		intron_variant	Intron 6 of 8		XP_047285946.1
GPC6	XM_017020302.2	c.460-17430T>G		intron_variant	Intron 3 of 5		XP_016875791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.1153-17430T>G		intron_variant	Intron 6 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32521 AN: 152048 Hom.: 3910 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.214 AC: 32514 AN: 152166 Hom.: 3911 Cov.: 33 AF XY: 0.218 AC XY: 16199 AN XY: 74386

African (AFR) AF: 0.110 AC: 4551 AN: 41544

American (AMR) AF: 0.261 AC: 3990 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1526 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1154 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3511 AN: 10564

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16357 AN: 67986

Other (OTH) AF: 0.200 AC: 423 AN: 2112

Alfa AF: 0.226 Hom.: 7445

Bravo AF: 0.207

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.40
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: rs9556365; hg19: chr13-95017238;