rs376394935

Variant names:

• chr6-56634571-G-A
• NM_001374736.1:c.3385C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-56634571-G-A
• chr6-56634571-G-T

Variant summary

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

The NM_001374736.1(DST):​c.3385C>T​(p.His1129Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DST NM_001374736.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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]

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 rank	MANE	Protein	UniProt
DST	NM_001374736.1	c.3385C>T	p.His1129Tyr	missense_variant	Exon 26 of 104	ENST00000680361.1	NP_001361665.1
DST	NM_001723.7	c.1774C>T	p.His592Tyr	missense_variant	Exon 12 of 24	ENST00000370765.11	NP_001714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361.1	c.3385C>T	p.His1129Tyr	missense_variant	Exon 26 of 104		NM_001374736.1	ENSP00000505098.1
DST	ENST00000370765.11	c.1774C>T	p.His592Tyr	missense_variant	Exon 12 of 24	1	NM_001723.7	ENSP00000359801.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;.;.;T;.;T;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.00020	T
MutationAssessor	Benign	1.4	.;.;.;L;.;.;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.9	D;D;.;D;D;D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.020	D;D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	.;.;.;.;.;D;D;D;D
Polyphen		1.0	D;.;.;.;.;D;.;D;D
Vest4		0.66
MVP		0.71
MPC		0.61
ClinPred		0.98	D
GERP RS		5.2
gMVP		0.29

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: chr6-56499369;