10-21515832-G-T

Variant names:

• chr10-21515832-G-T
• NM_207371.4:c.1991C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207371.4(SKIDA1):​c.1991C>A​(p.Ala664Glu) 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. 14/20 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: SKIDA1 NM_207371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15732953).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207371.4. 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
	SKIDA1	NM_207371.4	MANE Select	c.1991C>A	p.Ala664Glu	missense	Exon 4 of 4	NP_997254.3	Q1XH10-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIDA1	ENST00000449193.7	TSL:3 MANE Select	c.1991C>A	p.Ala664Glu	missense	Exon 4 of 4	ENSP00000410041.2	Q1XH10-1
	SKIDA1	ENST00000444772.3	TSL:5	c.1754C>A	p.Ala585Glu	missense	Exon 2 of 2	ENSP00000442432.1	Q1XH10-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
PhyloP100		2.0
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.052
Sift	Benign	0.27	T
Sift4G	Benign	0.14	T
Vest4		0.26
MutPred		0.20		Gain of solvent accessibility (P = 0.0411)
MVP		0.19
ClinPred		0.37	T
GERP RS		5.4
Varity_R		0.29
gMVP		0.15
Mutation Taster		=75/25	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

Other links and lift over

hg19: chr10-21804761;