rs113030903

Variant names:

• chr15-75675737-G-A
• rs113030903
• NM_001897.5:c.6782C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-75675737-G-A
• chr15-75675737-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001897.5(CSPG4):​c.6782C>T​(p.Thr2261Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,330 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CSPG4 NM_001897.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33

Genes affected

CSPG4 (HGNC:2466): (chondroitin sulfate proteoglycan 4) A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15632334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG4	NM_001897.5	c.6782C>T	p.Thr2261Ile	missense_variant	Exon 10 of 10	ENST00000308508.5	NP_001888.2
CSPG4	XM_047432196.1	c.5720C>T	p.Thr1907Ile	missense_variant	Exon 10 of 10		XP_047288152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPG4	ENST00000308508.5	c.6782C>T	p.Thr2261Ile	missense_variant	Exon 10 of 10	1	NM_001897.5	ENSP00000312506.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245608 Hom.: 0 AF XY: 0.00000754 AC XY: 1 AN XY: 132640

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451330 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720618

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.049
Sift	Benign	0.33	T
Sift4G	Benign	0.068	T
Polyphen		0.20	B
Vest4		0.10
MutPred		0.41		Loss of glycosylation at T2261 (P = 0.0093);
MVP		0.27
MPC		0.60
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.15
gMVP		0.46

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: rs113030903; hg19: chr15-75968078;