rs410851

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_006929.5(SKIC2):c.3201T>C(p.Tyr1067Tyr) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.97

Publications

37 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, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
trichohepatoenteric syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SKIC2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006929.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.085).

BP6

Variant 6-31968891-T-C is Benign according to our data. Variant chr6-31968891-T-C is described in ClinVar as Benign. ClinVar VariationId is 356345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 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.3201T>C	p.Tyr1067Tyr	synonymous	Exon 26 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.3201T>C	p.Tyr1067Tyr	synonymous	Exon 26 of 28	ENSP00000364543.2	Q15477
SKIC2	ENST00000465703.5	TSL:1	n.3837T>C		non_coding_transcript_exon	Exon 22 of 23
SKIC2	ENST00000962078.1		c.3303T>C	p.Tyr1101Tyr	synonymous	Exon 27 of 29	ENSP00000632137.1

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

121010

AN:

152034

Hom.:

48928

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.781

AC:

192300

AN:

246250

AF XY:

0.785

show subpopulations

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 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.:

AF XY:

0.728

AC XY:

528442

AN XY:

726350

show subpopulations

African (AFR)

AF:

0.927

AC:

31016

AN:

33474

American (AMR)

AF:

0.853

AC:

38126

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

22691

AN:

26128

East Asian (EAS)

AF:

0.689

AC:

27350

AN:

39680

South Asian (SAS)

AF:

0.897

AC:

77412

AN:

86254

European-Finnish (FIN)

AF:

0.732

AC:

38233

AN:

52234

Middle Eastern (MID)

AF:

0.894

AC:

5154

AN:

5768

European-Non Finnish (NFE)

AF:

0.691

AC:

768244

AN:

1111476

Other (OTH)

AF:

0.743

AC:

44853

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16897

33795

50692

67590

84487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19524

39048

58572

78096

97620

<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:

0.796

AC:

121137

AN:

152152

Hom.:

48995

Cov.:

AF XY:

0.801

AC XY:

59549

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.920

AC:

38221

AN:

41528

American (AMR)

AF:

0.848

AC:

12975

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

3032

AN:

3472

East Asian (EAS)

AF:

0.684

AC:

3528

AN:

5156

South Asian (SAS)

AF:

0.889

AC:

4290

AN:

4826

European-Finnish (FIN)

AF:

0.748

AC:

7912

AN:

10572

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.712

AC:

48387

AN:

67988

Other (OTH)

AF:

0.834

AC:

1756

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1252

2505

3757

5010

6262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.743

Hom.:

94570

Bravo

AF:

0.808

Asia WGS

AF:

0.851

AC:

2960

AN:

3478

EpiCase

AF:

0.745

EpiControl

AF:

0.763

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Trichohepatoenteric syndrome 2 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0090

(source)

DANN

Benign

0.58

PhyloP100

-3.0

PromoterAI

0.053

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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