rs3911893

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006929.5(SKIC2):c.2659G>A(p.Asp887Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 1,612,958 control chromosomes in the GnomAD database, including 1,696 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 286 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1410 hom. )

Consequence

SKIC2
NM_006929.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.420

Publications

26 publications found

Variant links:

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

SKIC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019786954).

BP6

Variant 6-31967790-G-A is Benign according to our data. Variant chr6-31967790-G-A is described in ClinVar as Benign. ClinVar VariationId is 356340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 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.2659G>A	p.Asp887Asn	missense	Exon 22 of 28	NP_008860.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SKIC2	ENST00000375394.7	TSL:1 MANE Select	c.2659G>A	p.Asp887Asn	missense	Exon 22 of 28	ENSP00000364543.2	Q15477
SKIC2	ENST00000465703.5	TSL:1	n.3158G>A		non_coding_transcript_exon	Exon 19 of 23
SKIC2	ENST00000962078.1		c.2761G>A	p.Asp921Asn	missense	Exon 23 of 29	ENSP00000632137.1

Frequencies

GnomAD3 genomes

AF:

0.0553

AC:

8409

AN:

152162

Hom.:

287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0766

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0557

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0378

Gnomad OTH

AF:

0.0659

GnomAD2 exomes

AF:

0.0518

AC:

12769

AN:

246348

AF XY:

0.0489

show subpopulations

Gnomad AFR exome

AF:

0.0790

Gnomad AMR exome

AF:

0.0548

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0398

Gnomad OTH exome

AF:

0.0535

GnomAD4 exome

AF:

0.0377

AC:

55109

AN:

1460678

Hom.:

1410

Cov.:

AF XY:

0.0374

AC XY:

27183

AN XY:

726664

show subpopulations

African (AFR)

AF:

0.0710

AC:

2377

AN:

33480

American (AMR)

AF:

0.0570

AC:

2550

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

2624

AN:

26136

East Asian (EAS)

AF:

0.0747

AC:

2965

AN:

39700

South Asian (SAS)

AF:

0.0370

AC:

3192

AN:

86258

European-Finnish (FIN)

AF:

0.0317

AC:

1657

AN:

52226

Middle Eastern (MID)

AF:

0.0498

AC:

287

AN:

5768

European-Non Finnish (NFE)

AF:

0.0328

AC:

36512

AN:

1112002

Other (OTH)

AF:

0.0488

AC:

2945

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

3225

6450

9674

12899

16124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1400

2800

4200

5600

7000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0553

AC:

8415

AN:

152280

Hom.:

286

Cov.:

AF XY:

0.0548

AC XY:

4081

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0766

AC:

3181

AN:

41540

American (AMR)

AF:

0.0609

AC:

932

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3472

East Asian (EAS)

AF:

0.108

AC:

562

AN:

5182

South Asian (SAS)

AF:

0.0556

AC:

268

AN:

4824

European-Finnish (FIN)

AF:

0.0332

AC:

353

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0378

AC:

2571

AN:

68024

Other (OTH)

AF:

0.0662

AC:

140

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

425

850

1275

1700

2125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0445

Hom.:

801

Bravo

AF:

0.0592

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0368

AC:

142

ESP6500AA

AF:

0.0748

AC:

226

ESP6500EA

AF:

0.0408

AC:

221

ExAC

AF:

0.0507

AC:

5989

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

EpiCase

AF:

0.0352

EpiControl

AF:

0.0402

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Trichohepatoenteric syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.64

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

0.42

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.73

REVEL

Benign

0.030

Sift

Benign

0.34

Sift4G

Benign

0.52

Polyphen

0.049

Vest4

0.037

MPC

0.37

ClinPred

0.0073

GERP RS

3.1

Varity_R

0.034

gMVP

0.39

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over