Variant rs397516943 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate

The ENST00000379802.8(DSP):c.478C>G(p.Arg160Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R160Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DSP
ENST00000379802.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.79

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.78

BP6

Variant 6-7559281-C-G is Benign according to our data. Variant chr6-7559281-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2937304.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DSP	NM_004415.4 linkuse as main transcript	c.478C>G	p.Arg160Gly	missense_variant	4/24	ENST00000379802.8	NP_004406.2
DSP	NM_001319034.2 linkuse as main transcript	c.478C>G	p.Arg160Gly	missense_variant	4/24		NP_001305963.1
DSP	NM_001008844.3 linkuse as main transcript	c.478C>G	p.Arg160Gly	missense_variant	4/24		NP_001008844.1
DSP	NM_001406591.1 linkuse as main transcript	c.478C>G	p.Arg160Gly	missense_variant	4/11		NP_001393520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8 linkuse as main transcript	c.478C>G	p.Arg160Gly	missense_variant	4/24	1	NM_004415.4	ENSP00000369129	P2	P15924-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251184

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Benign

0.0020

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.070

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.51

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.19

T;T

Polyphen

0.99

D;.

Vest4

0.86

MutPred

0.50

Loss of methylation at R160 (P = 0.0401);Loss of methylation at R160 (P = 0.0401);

MVP

0.96

MPC

0.93

ClinPred

0.69

GERP RS

3.8

Varity_R

0.29

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over