rs140889128

Variant names:

• chr1-2303939-C-G
• rs140889128
• NM_003036.4:c.1311C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-2303939-C-G
• chr1-2303939-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003036.4(SKI):​c.1311C>G​(p.Ala437Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,611,702 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A437A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SKI NM_003036.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.64
• Publications: 2 publications found

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]

SKI Gene-Disease associations (from GenCC):

• Shprintzen-Goldberg syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet, Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-2303939-C-G is Benign according to our data. Variant chr1-2303939-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS2: High AC in GnomAd4 at 62 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003036.4. 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
	SKI	NM_003036.4	MANE Select	c.1311C>G	p.Ala437Ala	synonymous	Exon 4 of 7	NP_003027.1	P12755

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKI	ENST00000378536.5	TSL:1 MANE Select	c.1311C>G	p.Ala437Ala	synonymous	Exon 4 of 7	ENSP00000367797.4	P12755
	SKI	ENST00000851187.1		c.1311C>G	p.Ala437Ala	synonymous	Exon 4 of 7	ENSP00000521247.1
	SKI	ENST00000507179.1	TSL:2	n.294C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000225 AC: 54 AN: 240128 AF XY: 0.000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000996

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000116 AC: 169 AN: 1459392 Hom.: 0 Cov.: 32 AF XY: 0.000105 AC XY: 76 AN XY: 726018

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00103 AC: 46 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000990 AC: 110 AN: 1111538

Other (OTH) AF: 0.000166 AC: 10 AN: 60228

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74470

African (AFR) AF: 0.0000962 AC: 4 AN: 41570

American (AMR) AF: 0.000588 AC: 9 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.0000362 Hom.: 0

Bravo AF: 0.000510

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	not specified (1)
-	-	1	Shprintzen-Goldberg syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.29
DANN	Benign	0.38
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140889128; hg19: chr1-2235378;