rs281875237

Variant names:

• chr6-31962012-T-G
• rs281875237
• NM_006929.5:c.1022T>G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_006929.5(SKIC2):​c.1022T>G​(p.Val341Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SKIC2 NM_006929.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 4.41

Genes affected

SKIC2 (HGNC:10898): (SKI2 subunit of superkiller complex) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a human homologue of yeast SKI2 and may be involved in antiviral activity by blocking translation of poly(A) deficient mRNAs. This gene is located in the class III region of the major histocompatibility complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874
• PP5: Variant 6-31962012-T-G is Pathogenic according to our data. Variant chr6-31962012-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 30070.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in UniProt as null. Variant chr6-31962012-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC2	NM_006929.5	c.1022T>G	p.Val341Gly	missense_variant	Exon 10 of 28	ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4	c.1022T>G	p.Val341Gly	missense_variant	Exon 10 of 25		XP_011513117.1
SKIC2	XM_047419259.1	c.1022T>G	p.Val341Gly	missense_variant	Exon 10 of 25		XP_047275215.1
SKIC2	XM_047419260.1	c.1022T>G	p.Val341Gly	missense_variant	Exon 10 of 24		XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7	c.1022T>G	p.Val341Gly	missense_variant	Exon 10 of 28	1	NM_006929.5	ENSP00000364543.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Trichohepatoenteric syndrome 2 Pathogenic:1

Apr 06, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Other:1

-

UniProtKB/Swiss-Prot

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Uncertain	0.085	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	3.9	H
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.80		Gain of disorder (P = 0.0269);
MVP		0.70
MPC		1.4
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.88
gMVP		0.93

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: rs281875237; hg19: chr6-31929789;