Genetic Variant SKA3:p.Val306Ile (chr13-21158125-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145061.6(SKA3):c.916G>A(p.Val306Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SKA3
NM_145061.6 missense, splice_region

Scores

Splicing: ADA: 0.001528

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.170

Publications

0 publications found

Variant links:

Genes affected

SKA3 (HGNC:20262): (spindle and kinetochore associated complex subunit 3) This gene encodes a component of the spindle and kinetochore-associated protein complex that regulates microtubule attachment to the kinetochores during mitosis. The encoded protein localizes to the outer kinetechore and may be required for normal chromosome segregation and cell division. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

SKA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026976317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145061.6. 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
	SKA3	NM_145061.6	MANE Select	c.916G>A	p.Val306Ile	missense splice_region	Exon 7 of 9	NP_659498.4
	SKA3	NM_001166017.2		c.916G>A	p.Val306Ile	missense splice_region	Exon 7 of 8	NP_001159489.1	Q8IX90-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SKA3	ENST00000314759.6	TSL:1 MANE Select	c.916G>A	p.Val306Ile	missense splice_region	Exon 7 of 9	ENSP00000319417.5	Q8IX90-1
SKA3	ENST00000921404.1		c.916G>A	p.Val306Ile	missense splice_region	Exon 7 of 9	ENSP00000591463.1
SKA3	ENST00000921408.1		c.859G>A	p.Val287Ile	missense splice_region	Exon 7 of 9	ENSP00000591467.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245618

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

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:

0.00000143

AC:

AN:

1401080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32172

American (AMR)

AF:

0.0000450

AC:

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25682

East Asian (EAS)

AF:

0.00

AC:

AN:

39314

South Asian (SAS)

AF:

0.00

AC:

AN:

84752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5412

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057866

Other (OTH)

AF:

0.00

AC:

AN:

58368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.60

M_CAP

Benign

0.0044

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.17

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.21

REVEL

Benign

0.033

Sift

Benign

0.62

Sift4G

Benign

0.50

Polyphen

0.0070

Vest4

0.015

MutPred

0.22

Gain of catalytic residue at L305 (P = 0)

MVP

0.19

MPC

0.10

ClinPred

0.026

GERP RS

1.7

Varity_R

0.027

gMVP

0.086

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0015

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over