rs454212

Variant names:

• chr6-31966595-C-A
• rs454212
• NM_006929.5:c.2203-114C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31966595-C-A
• chr6-31966595-C-G
• chr6-31966595-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006929.5(SKIC2):​c.2203-114C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 0 publications found

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]

SKIC2 Gene-Disease associations (from GenCC):

• trichohepatoenteric syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• trichohepatoenteric syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC2	NM_006929.5	c.2203-114C>A		intron_variant	Intron 18 of 27	ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4	c.2203-114C>A		intron_variant	Intron 18 of 24		XP_011513117.1
SKIC2	XM_047419259.1	c.2203-114C>A		intron_variant	Intron 18 of 24		XP_047275215.1
SKIC2	XM_047419260.1	c.2203-114C>A		intron_variant	Intron 18 of 23		XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7	c.2203-114C>A		intron_variant	Intron 18 of 27	1	NM_006929.5	ENSP00000364543.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 941514 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 479720

African (AFR) AF: 0.00 AC: 0 AN: 22710

American (AMR) AF: 0.00 AC: 0 AN: 34956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18620

East Asian (EAS) AF: 0.00 AC: 0 AN: 36894

South Asian (SAS) AF: 0.00 AC: 0 AN: 64700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 674618

Other (OTH) AF: 0.00 AC: 0 AN: 42404

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		-0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs454212; hg19: chr6-31934372;