rs547069600

Variant names:

• chr6-7541635-C-A
• rs547069600
• ENST00000418664.3:c.-281C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-7541635-C-A
• chr6-7541635-C-T

Variant summary

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

The ENST00000713903.1(DSP):​n.-281C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DSP ENST00000713903.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 2 publications found

Genes affected

DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DSP-AS1 (HGNC:56039): (DSP antisense RNA 1)

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=-0.56).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4	c.-281C>A		upstream_gene_variant		ENST00000379802.8	NP_004406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.-281C>A		upstream_gene_variant		1	NM_004415.4	ENSP00000369129.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 309460 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 160876

African (AFR) AF: 0.00 AC: 0 AN: 6898

American (AMR) AF: 0.00 AC: 0 AN: 8168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10238

East Asian (EAS) AF: 0.00 AC: 0 AN: 21632

South Asian (SAS) AF: 0.00 AC: 0 AN: 23786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 193310

Other (OTH) AF: 0.00 AC: 0 AN: 19178

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.58
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs547069600; hg19: chr6-7541868;