chr20-36771124-A-T

Position:

• chr20-36771124-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145315.2(DSN1):​c.104T>A​(p.Phe35Tyr) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSN1 NM_001145315.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.551

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

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=0.07958603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSN1	NM_001145315.2	c.104T>A	p.Phe35Tyr	missense_variant	3/11	ENST00000373750.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSN1	ENST00000373750.9	c.104T>A	p.Phe35Tyr	missense_variant	3/11	1	NM_001145315.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.104T>A (p.F35Y) alteration is located in exon 3 (coding exon 2) of the DSN1 gene. This alteration results from a T to A substitution at nucleotide position 104, causing the phenylalanine (F) at amino acid position 35 to be replaced by a tyrosine (Y). 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	0.10
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.025	T;.;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.39	T;T;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.68	N;N;N;N
REVEL	Benign	0.055
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.23	T;T;T;.
Polyphen		0.52	P;.;P;.
Vest4		0.14
MutPred		0.16		Gain of phosphorylation at F35 (P = 0.0265);.;Gain of phosphorylation at F35 (P = 0.0265);Gain of phosphorylation at F35 (P = 0.0265);
MVP		0.34
MPC		0.34
ClinPred		0.45	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.037
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-35399527;