rs410851

chr6-31968891-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006929.5(SKIC2):c.3201T>C(p.Tyr1067=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,612,252 control chromosomes in the GnomAD database, including 434,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48995 hom., cov: 32)
  • Exomes 𝑓: 0.72 (385106 hom.)
• Consequence: SKIC2 NM_006929.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.97

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-31968891-T-C is Benign according to our data. Variant chr6-31968891-T-C is described in ClinVar as [Benign]. Clinvar id is 356345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31968891-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC2	NM_006929.5	c.3201T>C	p.Tyr1067=	synonymous_variant	26/28	ENST00000375394.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7	c.3201T>C	p.Tyr1067=	synonymous_variant	26/28	1	NM_006929.5	P1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121010 AN: 152034 Hom.: 48928 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.832

GnomAD3 exomes AF: 0.781 AC: 192300 AN: 246250 Hom.: 76214 AF XY: 0.785 AC XY: 105395 AN XY: 134272

Gnomad AFR exome AF: 0.928

Gnomad AMR exome AF: 0.852

Gnomad ASJ exome AF: 0.872

Gnomad EAS exome AF: 0.689

Gnomad SAS exome AF: 0.901

Gnomad FIN exome AF: 0.740

Gnomad NFE exome AF: 0.720

Gnomad OTH exome AF: 0.778

GnomAD4 exome AF: 0.721 AC: 1053079 AN: 1460100 Hom.: 385106 Cov.: 60 AF XY: 0.728 AC XY: 528442 AN XY: 726350

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.853

Gnomad4 ASJ exome AF: 0.868

Gnomad4 EAS exome AF: 0.689

Gnomad4 SAS exome AF: 0.897

Gnomad4 FIN exome AF: 0.732

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.796 AC: 121137 AN: 152152 Hom.: 48995 Cov.: 32 AF XY: 0.801 AC XY: 59549 AN XY: 74378

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.834

Alfa AF: 0.736 Hom.: 65554

Bravo AF: 0.808

Asia WGS AF: 0.851 AC: 2960 AN: 3478

EpiCase AF: 0.745

EpiControl AF: 0.763

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Trichohepatoenteric syndrome 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0090
Dann	Benign	0.58
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8

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: rs410851; hg19: chr6-31936668; COSMIC: COSV61712720; COSMIC: COSV61712720;