6-31961022-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.545-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,578,740 control chromosomes in the GnomAD database, including 415,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47010 hom., cov: 32)
  • Exomes 𝑓: 0.71 (367998 hom.)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.140

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=-0.87).
• BP6: Variant 6-31961022-T-C is Benign according to our data. Variant chr6-31961022-T-C is described in ClinVar as [Benign]. Clinvar id is 1165036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31961022-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC2	NM_006929.5	c.545-19T>C		intron_variant		ENST00000375394.7
SKIC2	XM_011514815.4	c.545-19T>C		intron_variant
SKIC2	XM_047419259.1	c.545-19T>C		intron_variant
SKIC2	XM_047419260.1	c.545-19T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7	c.545-19T>C		intron_variant		1	NM_006929.5	P1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118626 AN: 152064 Hom.: 46954 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.818

GnomAD3 exomes AF: 0.762 AC: 188838 AN: 247734 Hom.: 73006 AF XY: 0.771 AC XY: 103889 AN XY: 134736

Gnomad AFR exome AF: 0.914

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.872

Gnomad EAS exome AF: 0.705

Gnomad SAS exome AF: 0.899

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.713 AC: 1017128 AN: 1426558 Hom.: 367998 Cov.: 28 AF XY: 0.721 AC XY: 512851 AN XY: 711788

Gnomad4 AFR exome AF: 0.911

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.866

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.895

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.687

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.780 AC: 118742 AN: 152182 Hom.: 47010 Cov.: 32 AF XY: 0.783 AC XY: 58228 AN XY: 74402

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.820

Alfa AF: 0.730 Hom.: 63335

Bravo AF: 0.787

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Trichohepatoenteric syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.5
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs419788; hg19: chr6-31928799;