Variant rs121912991 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000379802.8(DSP):c.991C>G(p.Gln331Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q331R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DSP
ENST00000379802.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.36

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:

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ACMG classification

Classification made for transcript

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=0.14678639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DSP	NM_004415.4 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/24	ENST00000379802.8	NP_004406.2
DSP	NM_001319034.2 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/24		NP_001305963.1
DSP	NM_001008844.3 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/24		NP_001008844.1
DSP	NM_001406591.1 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/11		NP_001393520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/24	1	NM_004415.4	ENSP00000369129	P2	P15924-1
DSP	ENST00000418664.2 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/24	1		ENSP00000396591	A2	P15924-2
DSP	ENST00000710359.1 linkuse as main transcript	c.991C>G	p.Gln331Glu	missense_variant	8/24			ENSP00000518230	A2
DSP	ENST00000682228.1 linkuse as main transcript	n.315C>G		non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251110

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

1461734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

-0.28

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.28

Sift

Benign

0.89

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.016

B;.

Vest4

0.54

MutPred

0.21

Loss of ubiquitination at K328 (P = 0.1);Loss of ubiquitination at K328 (P = 0.1);

MVP

0.34

MPC

0.76

ClinPred

0.48

GERP RS

5.4

Varity_R

0.20

gMVP

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over