rs1554108012

Positions:

• chr6-7579323-C-G
• chr6-7579323-C-T

Variant summary

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

The NM_004415.4(DSP):​c.3133C>G​(p.Arg1045Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,248 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DSP NM_004415.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSP	NM_004415.4	c.3133C>G	p.Arg1045Gly	missense_variant	23/24	ENST00000379802.8	NP_004406.2
DSP	NM_001319034.2	c.3133C>G	p.Arg1045Gly	missense_variant	23/24		NP_001305963.1
DSP	NM_001008844.3	c.3133C>G	p.Arg1045Gly	missense_variant	23/24		NP_001008844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.3133C>G	p.Arg1045Gly	missense_variant	23/24	1	NM_004415.4	ENSP00000369129.3
DSP	ENST00000418664.2	c.3133C>G	p.Arg1045Gly	missense_variant	23/24	1		ENSP00000396591.2
DSP	ENST00000710359.1	c.3133C>G	p.Arg1045Gly	missense_variant	23/24			ENSP00000518230.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74456

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Uncertain	0.073	D
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.96	P;.
Vest4		0.77
MutPred		0.21		Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);
MVP		0.85
MPC		0.93
ClinPred		0.96	D
GERP RS		3.7
Varity_R		0.28
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-7579556;