20-36754779-C-T

Variant names:

• chr20-36754779-C-T
• rs140941590
• NM_001145315.2:c.945G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001145315.2(DSN1):​c.945G>A​(p.Lys315Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,780 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (1 hom.)
• Consequence: DSN1 NM_001145315.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 5 publications found

Genes affected

DSN1 (HGNC:16165): (DSN1 component of MIS12 kinetochore complex) This gene encodes a kinetochore protein that functions as part of the minichromosome instability-12 centromere complex. The encoded protein is required for proper kinetochore assembly and progression through the cell cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145315.2. 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
	DSN1	NM_001145315.2	MANE Select	c.945G>A	p.Lys315Lys	synonymous	Exon 10 of 11	NP_001138787.1	Q9H410-1
	DSN1	NM_001145316.2		c.945G>A	p.Lys315Lys	synonymous	Exon 10 of 11	NP_001138788.1	Q9H410-1
	DSN1	NM_024918.4		c.945G>A	p.Lys315Lys	synonymous	Exon 10 of 11	NP_079194.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSN1	ENST00000373750.9	TSL:1 MANE Select	c.945G>A	p.Lys315Lys	synonymous	Exon 10 of 11	ENSP00000362855.4	Q9H410-1
	DSN1	ENST00000480153.5	TSL:1	n.1328G>A		non_coding_transcript_exon	Exon 9 of 10
	DSN1	ENST00000426836.5	TSL:2	c.945G>A	p.Lys315Lys	synonymous	Exon 10 of 11	ENSP00000389810.1	Q9H410-1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 251120 AF XY: 0.000155

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00201

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461620 Hom.: 1 Cov.: 30 AF XY: 0.0000509 AC XY: 37 AN XY: 727136

African (AFR) AF: 0.0000896 AC: 3 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00126 AC: 50 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111822

Other (OTH) AF: 0.000431 AC: 26 AN: 60376

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74332

African (AFR) AF: 0.000169 AC: 7 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	0.98
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs140941590; hg19: chr20-35383182;