rs1553201549

Variant names:

• chr1-2306689-A-G
• rs1553201549
• NM_003036.4:c.2111A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-2306689-A-G
• chr1-2306689-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003036.4(SKI):​c.2111A>G​(p.Glu704Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E704E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SKI NM_003036.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20626542).

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.2111A>G	p.Glu704Gly	missense	Exon 7 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.2111A>G	p.Glu704Gly	missense	Exon 7 of 7	ENSP00000367797.4	P12755
	SKI	ENST00000851187.1		c.2117A>G	p.Glu706Gly	missense	Exon 7 of 7	ENSP00000521247.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Shprintzen-Goldberg syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.16		Gain of MoRF binding (P = 0.0458)
MVP		0.81
MPC		1.3
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.17
gMVP		0.44
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1553201549; hg19: chr1-2238128;