6-56851277-C-A

Variant names:

• chr6-56851277-C-A
• rs13207768
• NM_001374736.1:c.625+120G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001374736.1(DST):​c.625+120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 891,750 control chromosomes in the GnomAD database, including 12,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1569 hom., cov: 33)
  • Exomes 𝑓: 0.16 (10652 hom.)
• Consequence: DST NM_001374736.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.151
• Publications: 3 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 6-56851277-C-A is Benign according to our data. Variant chr6-56851277-C-A is described in ClinVar as Benign. ClinVar VariationId is 1232891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

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.625+120G>T		intron	N/A	NP_001361665.1	A0A7P0T890
	DST	NM_001374734.1		c.652+120G>T		intron	N/A	NP_001361663.1
	DST	NM_001374722.1		c.625+120G>T		intron	N/A	NP_001361651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	ENST00000680361.1	MANE Select	c.625+120G>T		intron	N/A	ENSP00000505098.1	A0A7P0T890
	DST	ENST00000449297.7	TSL:5	c.625+120G>T		intron	N/A	ENSP00000393082.3	Q5T0V7
	DST	ENST00000312431.10	TSL:5	c.211+120G>T		intron	N/A	ENSP00000307959.7	F6QMI7

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18471 AN: 152122 Hom.: 1569 Cov.: 33

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.158 AC: 117085 AN: 739506 Hom.: 10652 Cov.: 10 AF XY: 0.154 AC XY: 57850 AN XY: 375642

African (AFR) AF: 0.0260 AC: 463 AN: 17824

American (AMR) AF: 0.0908 AC: 1954 AN: 21528

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 1764 AN: 15926

East Asian (EAS) AF: 0.000339 AC: 11 AN: 32414

South Asian (SAS) AF: 0.0567 AC: 2987 AN: 52654

European-Finnish (FIN) AF: 0.206 AC: 8856 AN: 42928

Middle Eastern (MID) AF: 0.146 AC: 377 AN: 2576

European-Non Finnish (NFE) AF: 0.184 AC: 95547 AN: 518468

Other (OTH) AF: 0.146 AC: 5126 AN: 35188

GnomAD4 genome AF: 0.121 AC: 18458 AN: 152244 Hom.: 1569 Cov.: 33 AF XY: 0.120 AC XY: 8907 AN XY: 74444

African (AFR) AF: 0.0302 AC: 1255 AN: 41572

American (AMR) AF: 0.0968 AC: 1480 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2218 AN: 10584

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12410 AN: 68010

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.142 Hom.: 898

Bravo AF: 0.111

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13207768; hg19: chr6-56716075;