NM_003036.4:c.15A>T

Variant names:

• chr1-2228781-A-T
• NM_003036.4:c.15A>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003036.4(SKI):​c.15A>T​(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,142,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SKI NM_003036.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=0.195 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKI	NM_003036.4	c.15A>T	p.Ala5Ala	synonymous_variant	Exon 1 of 7	ENST00000378536.5	NP_003027.1
SKI	XM_005244775.4	c.15A>T	p.Ala5Ala	synonymous_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.15A>T	p.Ala5Ala	synonymous_variant	Exon 1 of 7	1	NM_003036.4	ENSP00000367797.4
SKI	ENST00000704337.1	n.137+1257A>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1142988 Hom.: 0 Cov.: 31 AF XY: 0.00000357 AC XY: 2 AN XY: 560632

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: 0.0000362

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
BayesDel_noAF	Benign	-0.94
CADD	Benign	11
DANN	Benign	0.47
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.4

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-2160220;