6-31965741-T-C

Variant names:

• chr6-31965741-T-C
• rs492899
• NM_006929.5:c.1972-42T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006929.5(SKIC2):​c.1972-42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,252,492 control chromosomes in the GnomAD database, including 9,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2235 hom., cov: 33)
  • Exomes 𝑓: 0.10 (7410 hom.)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30
• Publications: 42 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-31965741-T-C is Benign according to our data. Variant chr6-31965741-T-C is described in ClinVar as Benign. ClinVar VariationId is 1228348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 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.1972-42T>C		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.1972-42T>C		intron	N/A	ENSP00000364543.2
	SKIC2	ENST00000465703.5	TSL:1	n.2471-42T>C		intron	N/A
	SKIC2	ENST00000962078.1		c.1972-42T>C		intron	N/A	ENSP00000632137.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22847 AN: 152086 Hom.: 2224 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.119 AC: 27925 AN: 235250 AF XY: 0.123

Gnomad AFR exome AF: 0.273

Gnomad AMR exome AF: 0.0791

Gnomad ASJ exome AF: 0.0799

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.0858

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.102 AC: 112265 AN: 1100288 Hom.: 7410 Cov.: 15 AF XY: 0.106 AC XY: 59481 AN XY: 558796

African (AFR) AF: 0.272 AC: 7242 AN: 26668

American (AMR) AF: 0.0855 AC: 3715 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 1916 AN: 22954

East Asian (EAS) AF: 0.0826 AC: 3112 AN: 37690

South Asian (SAS) AF: 0.209 AC: 16144 AN: 77102

European-Finnish (FIN) AF: 0.149 AC: 7652 AN: 51230

Middle Eastern (MID) AF: 0.257 AC: 1298 AN: 5048

European-Non Finnish (NFE) AF: 0.0835 AC: 65814 AN: 787942

Other (OTH) AF: 0.111 AC: 5372 AN: 48204

GnomAD4 genome AF: 0.150 AC: 22899 AN: 152204 Hom.: 2235 Cov.: 33 AF XY: 0.154 AC XY: 11463 AN XY: 74432

African (AFR) AF: 0.269 AC: 11165 AN: 41488

American (AMR) AF: 0.119 AC: 1817 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 267 AN: 3468

East Asian (EAS) AF: 0.0993 AC: 514 AN: 5176

South Asian (SAS) AF: 0.188 AC: 907 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1729 AN: 10608

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.0873 AC: 5939 AN: 68020

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.104 Hom.: 4296

Bravo AF: 0.149

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Trichohepatoenteric syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.030
DANN	Benign	0.52
PhyloP100		-2.3
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: rs492899; hg19: chr6-31933518;