10-21515500-C-A

Variant names:

• chr10-21515500-C-A
• rs866254958
• NM_207371.4:c.2323G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207371.4(SKIDA1):​c.2323G>T​(p.Ala775Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: SKIDA1 NM_207371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

Genes affected

SKIDA1 (HGNC:32697): (SKI/DACH domain containing 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31343216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIDA1	NM_207371.4	c.2323G>T	p.Ala775Ser	missense_variant	Exon 4 of 4	ENST00000449193.7	NP_997254.3
SKIDA1	XM_047425204.1	c.2323G>T	p.Ala775Ser	missense_variant	Exon 2 of 2		XP_047281160.1
SKIDA1	XM_047425205.1	c.2323G>T	p.Ala775Ser	missense_variant	Exon 2 of 2		XP_047281161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIDA1	ENST00000449193.7	c.2323G>T	p.Ala775Ser	missense_variant	Exon 4 of 4	3	NM_207371.4	ENSP00000410041.2
SKIDA1	ENST00000444772.3	c.2086G>T	p.Ala696Ser	missense_variant	Exon 2 of 2	5		ENSP00000442432.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

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

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2323G>T (p.A775S) alteration is located in exon 4 (coding exon 1) of the SKIDA1 gene. This alteration results from a G to T substitution at nucleotide position 2323, causing the alanine (A) at amino acid position 775 to be replaced by a serine (S). 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	0.62
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.37	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.090	T;D
Sift4G	Benign	0.16	T;T
Vest4		0.44
MutPred		0.36		Gain of phosphorylation at A775 (P = 0.0205);.;
MVP		0.21
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.18
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs866254958; hg19: chr10-21804429;