NM_207371.4:c.2057A>G

Variant names:

• chr10-21515766-T-C
• rs2032180127
• NM_207371.4:c.2057A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_207371.4(SKIDA1):​c.2057A>G​(p.Lys686Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,696 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SKIDA1 NM_207371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.171653).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

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.2057A>G	p.Lys686Arg	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.2057A>G	p.Lys686Arg	missense	Exon 4 of 4	ENSP00000410041.2	Q1XH10-1
	SKIDA1	ENST00000444772.3	TSL:5	c.1820A>G	p.Lys607Arg	missense	Exon 2 of 2	ENSP00000442432.1	Q1XH10-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461696 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111866

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.070	T
Sift4G	Benign	0.25	T
Vest4		0.25
MutPred		0.38		Loss of ubiquitination at K686 (P = 0.0127)
MVP		0.21
ClinPred		0.73	D
GERP RS		6.1
Varity_R		0.11
gMVP		0.26
Mutation Taster		=95/5	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

dbSNP: rs2032180127; hg19: chr10-21804695;