rs1057520161

Variant names:

• chr1-2304323-C-A
• NM_003036.4:c.1505C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2304323-C-A
• chr1-2304323-C-G
• chr1-2304323-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003036.4(SKI):​c.1505C>A​(p.Pro502Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,360 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P502L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SKI NM_003036.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKI	NM_003036.4	c.1505C>A	p.Pro502Gln	missense_variant	Exon 5 of 7	ENST00000378536.5	NP_003027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKI	ENST00000378536.5	c.1505C>A	p.Pro502Gln	missense_variant	Exon 5 of 7	1	NM_003036.4	ENSP00000367797.4
SKI	ENST00000507179.1	n.494C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399360 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 690222

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	35
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.55
Sift	Benign	0.041	D
Sift4G	Benign	0.085	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.29		Loss of glycosylation at P502 (P = 0.029);
MVP		0.71
MPC		0.75
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.98		Position offset: 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: chr1-2235762;