DSN1 p.Gln311His

Variant names:

• chr20-36754791-C-A
• NM_001145315.2:c.933G>T
• DSN1 p.Gln311His

Your query was ambiguous. Multiple possible variants found:

• chr20-36754791-C-A
• chr20-36754791-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145315.2(DSN1):​c.933G>T​(p.Gln311His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q311R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DSN1 NM_001145315.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.933G>T	p.Gln311His	missense	Exon 10 of 11	NP_001138787.1	Q9H410-1
	DSN1	NM_001145316.2		c.933G>T	p.Gln311His	missense	Exon 10 of 11	NP_001138788.1	Q9H410-1
	DSN1	NM_024918.4		c.933G>T	p.Gln311His	missense	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.933G>T	p.Gln311His	missense	Exon 10 of 11	ENSP00000362855.4	Q9H410-1
	DSN1	ENST00000480153.5	TSL:1	n.1316G>T		non_coding_transcript_exon	Exon 9 of 10
	DSN1	ENST00000426836.5	TSL:2	c.933G>T	p.Gln311His	missense	Exon 10 of 11	ENSP00000389810.1	Q9H410-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.62
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.013	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.14
Mutation Taster		=69/31	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-35383194;