6-7567795-G-T

Position:

• chr6-7567795-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The ENST00000379802.8(DSP):​c.1155G>T​(p.Ala385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,636 control chromosomes in the GnomAD database, including 1 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. Synonymous variant affecting the same amino acid position (i.e. A385A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (1 hom.)
• Consequence: DSP ENST00000379802.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSP	NM_004415.4	c.1155G>T	p.Ala385=	synonymous_variant	10/24	ENST00000379802.8	NP_004406.2
DSP	NM_001319034.2	c.1155G>T	p.Ala385=	synonymous_variant	10/24		NP_001305963.1
DSP	NM_001008844.3	c.1155G>T	p.Ala385=	synonymous_variant	10/24		NP_001008844.1
DSP	NM_001406591.1	c.1155G>T	p.Ala385=	synonymous_variant	10/11		NP_001393520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.1155G>T	p.Ala385=	synonymous_variant	10/24	1	NM_004415.4	ENSP00000369129	P2
DSP	ENST00000418664.2	c.1155G>T	p.Ala385=	synonymous_variant	10/24	1		ENSP00000396591	A2
DSP	ENST00000710359.1	c.1155G>T	p.Ala385=	synonymous_variant	10/24			ENSP00000518230	A2
DSP	ENST00000682228.1	n.810G>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251194 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135770

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: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461636 Hom.: 1 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727126

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs140488069; hg19: chr6-7568028;