chr1-2228788-C-A

Variant names:

• chr1-2228788-C-A
• rs1254990952
• NM_003036.4:c.22C>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_003036.4(SKI):​c.22C>A​(p.Arg8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,163,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: SKI NM_003036.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886

Genes affected

SKI (HGNC:10896): (SKI proto-oncogene) This gene encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene. It functions as a repressor of TGF-beta signaling, and may play a role in neural tube development and muscle differentiation. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 1-2228788-C-A is Benign according to our data. Variant chr1-2228788-C-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKI	NM_003036.4	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 7	ENST00000378536.5	NP_003027.1
SKI	XM_005244775.4	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 7		XP_005244832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKI	ENST00000378536.5	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 7	1	NM_003036.4	ENSP00000367797.4
SKI	ENST00000704337.1	n.137+1264C>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000529 AC: 4 AN: 75616 Hom.: 0 AF XY: 0.0000229 AC XY: 1 AN XY: 43692

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000182

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000516 AC: 6 AN: 1163210 Hom.: 0 Cov.: 31 AF XY: 0.00000700 AC XY: 4 AN XY: 571586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Benign	0.26	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.24
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.011	D
Polyphen		0.96	D
Vest4		0.49
MutPred		0.24		Gain of glycosylation at R8 (P = 8e-04);
MVP		0.67
MPC		1.6
ClinPred		0.16	T
GERP RS		0.70
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.5
Varity_R		0.13
gMVP		0.52

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: rs1254990952; hg19: chr1-2160227;