chr6-56851594-T-C

Variant names:

• chr6-56851594-T-C
• NM_001374736.1:c.428A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001374736.1(DST):​c.428A>G​(p.Asn143Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DST NM_001374736.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• Publications: 0 publications found

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]

DST-AS1 (HGNC:40098): (DST antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24857354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374736.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	NM_001374736.1	MANE Select	c.428A>G	p.Asn143Ser	missense	Exon 4 of 104	NP_001361665.1	A0A7P0T890
	DST	NM_001374734.1		c.455A>G	p.Asn152Ser	missense	Exon 4 of 103	NP_001361663.1
	DST	NM_001374722.1		c.428A>G	p.Asn143Ser	missense	Exon 4 of 103	NP_001361651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	ENST00000680361.1	MANE Select	c.428A>G	p.Asn143Ser	missense	Exon 4 of 104	ENSP00000505098.1	A0A7P0T890
	DST	ENST00000449297.7	TSL:5	c.428A>G	p.Asn143Ser	missense	Exon 4 of 95	ENSP00000393082.3	Q5T0V7
	DST	ENST00000312431.10	TSL:5	c.14A>G	p.Asn5Ser	missense	Exon 2 of 95	ENSP00000307959.7	F6QMI7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.25	D
PhyloP100		3.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.24
Sift	Benign	0.16	T
Sift4G	Uncertain	0.049	D
Vest4		0.34
MutPred		0.20		Gain of phosphorylation at N143 (P = 0.0067)
MVP		0.46
ClinPred		0.84	D
GERP RS		5.8
PromoterAI		-0.037	Neutral
gMVP		0.047
Mutation Taster		=90/10	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr6-56716392;