rs592229

Variant names:

• chr6-31962664-G-T
• rs592229
• NM_006929.5:c.1212-50G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31962664-G-T
• chr6-31962664-G-A
• chr6-31962664-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006929.5(SKIC2):​c.1212-50G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,603,580 control chromosomes in the GnomAD database, including 258,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29300 hom., cov: 29)
  • Exomes 𝑓: 0.56 (229085 hom.)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122
• Publications: 65 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• trichohepatoenteric syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-31962664-G-T is Benign according to our data. Variant chr6-31962664-G-T is described in ClinVar as Benign. ClinVar VariationId is 1182354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006929.5. 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
	SKIC2	NM_006929.5	MANE Select	c.1212-50G>T		intron	N/A	NP_008860.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	ENST00000375394.7	TSL:1 MANE Select	c.1212-50G>T		intron	N/A	ENSP00000364543.2	Q15477
	SKIC2	ENST00000465703.5	TSL:1	n.1525-50G>T		intron	N/A
	SKIC2	ENST00000962078.1		c.1212-50G>T		intron	N/A	ENSP00000632137.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93440 AN: 151510 Hom.: 29264 Cov.: 29

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.649

GnomAD2 exomes AF: 0.609 AC: 150431 AN: 247154 AF XY: 0.614

Gnomad AFR exome AF: 0.714

Gnomad AMR exome AF: 0.601

Gnomad ASJ exome AF: 0.783

Gnomad EAS exome AF: 0.580

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.556 AC: 807154 AN: 1451952 Hom.: 229085 Cov.: 30 AF XY: 0.562 AC XY: 406097 AN XY: 722678

African (AFR) AF: 0.712 AC: 23710 AN: 33318

American (AMR) AF: 0.607 AC: 27099 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 20209 AN: 25988

East Asian (EAS) AF: 0.493 AC: 19513 AN: 39610

South Asian (SAS) AF: 0.681 AC: 58632 AN: 86068

European-Finnish (FIN) AF: 0.590 AC: 30916 AN: 52368

Middle Eastern (MID) AF: 0.787 AC: 4522 AN: 5746

European-Non Finnish (NFE) AF: 0.533 AC: 588369 AN: 1104164

Other (OTH) AF: 0.569 AC: 34184 AN: 60052

GnomAD4 genome AF: 0.617 AC: 93530 AN: 151628 Hom.: 29300 Cov.: 29 AF XY: 0.620 AC XY: 45897 AN XY: 74064

African (AFR) AF: 0.702 AC: 29010 AN: 41302

American (AMR) AF: 0.603 AC: 9195 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2709 AN: 3462

East Asian (EAS) AF: 0.540 AC: 2780 AN: 5146

South Asian (SAS) AF: 0.685 AC: 3277 AN: 4784

European-Finnish (FIN) AF: 0.614 AC: 6461 AN: 10524

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37785 AN: 67858

Other (OTH) AF: 0.652 AC: 1373 AN: 2106

Alfa AF: 0.579 Hom.: 90712

Bravo AF: 0.622

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.67
DANN	Benign	0.73
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs592229; hg19: chr6-31930441; COSMIC: COSV64813539; COSMIC: COSV64813539;