NM_006929.5:c.545-19T>C

Variant names:

• chr6-31961022-T-C
• rs419788
• NM_006929.5:c.545-19T>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.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
• Publications: 63 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=-0.87).
• BP6: Variant 6-31961022-T-C is Benign according to our data. Variant chr6-31961022-T-C is described in ClinVar as Benign. ClinVar VariationId is 1165036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	NM_006929.5	MANE Select	c.545-19T>C		intron	N/A	NP_008860.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	ENST00000375394.7	TSL:1 MANE Select	c.545-19T>C		intron	N/A	ENSP00000364543.2
	SKIC2	ENST00000465703.5	TSL:1	n.597-19T>C		intron	N/A
	SKIC2	ENST00000697840.1		c.562T>C	p.Ser188Pro	missense	Exon 7 of 28	ENSP00000513458.1

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

GnomAD2 exomes AF: 0.762 AC: 188838 AN: 247734 AF XY: 0.771

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 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

African (AFR) AF: 0.911 AC: 29773 AN: 32664

American (AMR) AF: 0.736 AC: 32887 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 22452 AN: 25922

East Asian (EAS) AF: 0.661 AC: 26125 AN: 39530

South Asian (SAS) AF: 0.895 AC: 76428 AN: 85410

European-Finnish (FIN) AF: 0.725 AC: 37959 AN: 52346

Middle Eastern (MID) AF: 0.894 AC: 5087 AN: 5690

European-Non Finnish (NFE) AF: 0.687 AC: 742887 AN: 1081132

Other (OTH) AF: 0.735 AC: 43530 AN: 59190

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

African (AFR) AF: 0.906 AC: 37624 AN: 41524

American (AMR) AF: 0.746 AC: 11416 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3027 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3520 AN: 5176

South Asian (SAS) AF: 0.887 AC: 4278 AN: 4824

European-Finnish (FIN) AF: 0.741 AC: 7838 AN: 10582

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48270 AN: 67990

Other (OTH) AF: 0.820 AC: 1733 AN: 2114

Alfa AF: 0.733 Hom.: 162903

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Trichohepatoenteric syndrome 2 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.79
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs419788; hg19: chr6-31928799;