rs397516928

Variant names:

• chr6-7577031-A-C
• NM_004415.4:c.2866A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-7577031-A-C
• chr6-7577031-A-T

Variant summary

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

The NM_004415.4(DSP):​c.2866A>C​(p.Asn956His) variant causes a missense 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)
• Consequence: DSP NM_004415.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14889896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4	c.2866A>C	p.Asn956His	missense_variant	Exon 20 of 24	ENST00000379802.8	NP_004406.2
DSP	NM_001319034.2	c.2866A>C	p.Asn956His	missense_variant	Exon 20 of 24		NP_001305963.1
DSP	NM_001008844.3	c.2866A>C	p.Asn956His	missense_variant	Exon 20 of 24		NP_001008844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.2866A>C	p.Asn956His	missense_variant	Exon 20 of 24	1	NM_004415.4	ENSP00000369129.3
DSP	ENST00000418664.2	c.2866A>C	p.Asn956His	missense_variant	Exon 20 of 24	1		ENSP00000396591.2
DSP	ENST00000710359.1	c.2866A>C	p.Asn956His	missense_variant	Exon 20 of 24			ENSP00000518230.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.0011
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.079
Sift	Benign	0.055	T;D
Sift4G	Benign	0.13	T;T
Polyphen		0.0	B;.
Vest4		0.31
MutPred		0.25		Loss of ubiquitination at K959 (P = 0.1191);Loss of ubiquitination at K959 (P = 0.1191);
MVP		0.45
MPC		0.22
ClinPred		0.44	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.085
gMVP		0.21

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: chr6-7577264;