NM_005708.5:c.320-6C>G

Variant names:

• chr13-93830148-C-G
• rs377404400
• NM_005708.5:c.320-6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005708.5(GPC6):​c.320-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPC6 NM_005708.5 splice_region, intron
• Scores: Splicing: ADA: 0.005905
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670
• Publications: 0 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-AS2 (HGNC:39910): (GPC6 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.320-6C>G		splice_region intron	N/A	NP_005699.1	Q9Y625
	GPC6-AS2	NR_046536.1		n.380+668G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	ENST00000377047.9	TSL:1 MANE Select	c.320-6C>G		splice_region intron	N/A	ENSP00000366246.3	Q9Y625
	GPC6-AS2	ENST00000445540.1	TSL:5	n.228+668G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454648 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723704

African (AFR) AF: 0.00 AC: 0 AN: 33196

American (AMR) AF: 0.00 AC: 0 AN: 44068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 85556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107644

Other (OTH) AF: 0.00 AC: 0 AN: 60050

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.7
DANN	Benign	0.78
PhyloP100		-0.067

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0059
dbscSNV1_RF	Benign	0.096
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: rs377404400; hg19: chr13-94482401;