rs4715631

Variant summary

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

The NM_001374736.1(DST):​c.16045A>T​(p.Thr5349Ser) 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. 12/17 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. T5349A) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DST
NM_001374736.1 missense

Scores

1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74
Variant links:
Genes affected
DST (HGNC:1090): (dystonin) This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been reported that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration. [provided by RefSeq, Mar 2010]

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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=0.09450793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DSTNM_001374736.1 linkc.16045A>T p.Thr5349Ser missense_variant Exon 61 of 104 ENST00000680361.1 NP_001361665.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DSTENST00000680361.1 linkc.16045A>T p.Thr5349Ser missense_variant Exon 61 of 104 NM_001374736.1 ENSP00000505098.1 A0A7P0T890

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
58
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
15
DANN
Benign
0.82
DEOGEN2
Benign
0.019
.;.;.;.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.94
D;D;D;T;T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.095
T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.8
N;N;.;N;N
REVEL
Benign
0.038
Sift
Benign
0.15
T;T;.;T;T
Polyphen
0.0020
B;.;.;.;.
Vest4
0.12
MVP
0.33
MPC
0.11
ClinPred
0.13
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.076

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.

Other links and lift over

dbSNP: rs4715631; hg19: chr6-56417545; API