Variant chr20-36768033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145315.2(DSN1):c.365G>A(p.Arg122Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DSN1
NM_001145315.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

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]

DSN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2406219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSN1	NM_001145315.2 link	c.365G>A	p.Arg122Gln	missense_variant	4/11	ENST00000373750.9	NP_001138787.1	Q9H410-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSN1	ENST00000373750.9 link	c.365G>A	p.Arg122Gln	missense_variant	4/11	1	NM_001145315.2	ENSP00000362855.4		Q9H410-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251434

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.365G>A (p.R122Q) alteration is located in exon 4 (coding exon 3) of the DSN1 gene. This alteration results from a G to A substitution at nucleotide position 365, causing the arginine (R) at amino acid position 122 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T;.;T;.;T;T

Eigen

Benign

0.019

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

D;D;D;.;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.24

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.;L;.;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.14

T;T;T;T;T;T;T

Sift4G

Benign

0.25

T;T;T;T;T;.;.

Polyphen

0.67

P;.;.;P;.;.;.

Vest4

0.45

MutPred

0.57

Loss of phosphorylation at S125 (P = 0.0562);.;.;Loss of phosphorylation at S125 (P = 0.0562);.;.;Loss of phosphorylation at S125 (P = 0.0562);

MVP

0.69

MPC

0.87

ClinPred

0.86

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over