rs769721648

Variant names:

• chr20-36762474-C-T
• rs769721648
• NM_001145315.2:c.577G>A

Variant summary

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

The NM_001145315.2(DSN1):​c.577G>A​(p.Glu193Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DSN1 NM_001145315.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.577G>A	p.Glu193Lys	missense	Exon 6 of 11	NP_001138787.1	Q9H410-1
	DSN1	NM_001145316.2		c.577G>A	p.Glu193Lys	missense	Exon 6 of 11	NP_001138788.1	Q9H410-1
	DSN1	NM_024918.4		c.577G>A	p.Glu193Lys	missense	Exon 6 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.577G>A	p.Glu193Lys	missense	Exon 6 of 11	ENSP00000362855.4	Q9H410-1
	DSN1	ENST00000480153.5	TSL:1	n.960G>A		non_coding_transcript_exon	Exon 5 of 10
	DSN1	ENST00000426836.5	TSL:2	c.577G>A	p.Glu193Lys	missense	Exon 6 of 11	ENSP00000389810.1	Q9H410-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 0.0000957 AC: 24 AN: 250760 AF XY: 0.0000811

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000699

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461150 Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12 AN XY: 726858

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.000583 AC: 26 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111722

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.064
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.055	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.23	B
Vest4		0.34
MutPred		0.78		Gain of methylation at E193 (P = 0.0148)
MVP		0.71
MPC		0.38
ClinPred		0.11	T
GERP RS		3.9
Varity_R		0.28
gMVP		0.14
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.28		Position offset: -13

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

Other links and lift over

dbSNP: rs769721648; hg19: chr20-35390877;