chr13-21168101-C-T

Variant names:

• chr13-21168101-C-T
• NM_145061.6:c.630G>A

Variant summary

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

The NM_145061.6(SKA3):​c.630G>A​(p.Met210Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SKA3 NM_145061.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKA3	NM_145061.6	c.630G>A	p.Met210Ile	missense_variant	Exon 4 of 9	ENST00000314759.6	NP_659498.4
SKA3	NM_001166017.2	c.630G>A	p.Met210Ile	missense_variant	Exon 4 of 8		NP_001159489.1
SKA3	XM_011534994.3	c.510G>A	p.Met170Ile	missense_variant	Exon 4 of 9		XP_011533296.1
SKA3	XM_005266288.5	c.384G>A	p.Met128Ile	missense_variant	Exon 3 of 8		XP_005266345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKA3	ENST00000314759.6	c.630G>A	p.Met210Ile	missense_variant	Exon 4 of 9	1	NM_145061.6	ENSP00000319417.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.630G>A (p.M210I) alteration is located in exon 4 (coding exon 4) of the SKA3 gene. This alteration results from a G to A substitution at nucleotide position 630, causing the methionine (M) at amino acid position 210 to be replaced by an isoleucine (I). 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	Pathogenic	0.84
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.99	D;D
Vest4		0.72
MutPred		0.40		Gain of methylation at K209 (P = 0.0356);Gain of methylation at K209 (P = 0.0356);
MVP		0.48
MPC		0.60
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.83
gMVP		0.38

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: chr13-21742240;