chr5-95490951-C-A

Variant names:

Variant summary

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

The NM_014639.4(SKIC3):c.3888G>T(p.Arg1296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,666 control chromosomes in the GnomAD database, including 24,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4659 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19870 hom. )

Consequence

SKIC3
NM_014639.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.33

Publications

38 publications found

Variant links:

Genes affected

SKIC3 (HGNC:23639): (SKI3 subunit of superkiller complex) This gene encodes a protein with twenty tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Mutations in this gene are associated with trichohepatoenteric syndrome. [provided by RefSeq, Jul 2010]

SKIC3 Gene-Disease associations (from GenCC):

trichohepatoenteric syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
trichohepatoenteric syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SKIC3 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=0.0020938218).

BP6

Variant 5-95490951-C-A is Benign according to our data. Variant chr5-95490951-C-A is described in ClinVar as [Benign]. Clinvar id is 1166551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC3	NM_014639.4 link	c.3888G>T	p.Arg1296Ser	missense_variant	Exon 37 of 43	ENST00000358746.7	NP_055454.1	Q6PGP7
SKIC3	XM_047417937.1 link	c.3888G>T	p.Arg1296Ser	missense_variant	Exon 37 of 43		XP_047273893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC3	ENST00000358746.7 link	c.3888G>T	p.Arg1296Ser	missense_variant	Exon 37 of 43	1	NM_014639.4	ENSP00000351596.3		Q6PGP7

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33494

AN:

151882

Hom.:

4648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.226

GnomAD2 exomes

AF:

0.179

AC:

44893

AN:

251232

AF XY:

0.177

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.155

AC:

226758

AN:

1461666

Hom.:

19870

Cov.:

AF XY:

0.157

AC XY:

114319

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.395

AC:

13225

AN:

33472

American (AMR)

AF:

0.168

AC:

7522

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

8541

AN:

26128

East Asian (EAS)

AF:

0.137

AC:

5426

AN:

39690

South Asian (SAS)

AF:

0.197

AC:

17002

AN:

86258

European-Finnish (FIN)

AF:

0.117

AC:

6245

AN:

53396

Middle Eastern (MID)

AF:

0.294

AC:

1693

AN:

5768

European-Non Finnish (NFE)

AF:

0.141

AC:

156795

AN:

1111848

Other (OTH)

AF:

0.171

AC:

10309

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

10529

21058

31587

42116

52645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5732

11464

17196

22928

28660

<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:

0.221

AC:

33533

AN:

152000

Hom.:

4659

Cov.:

AF XY:

0.219

AC XY:

16312

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.388

AC:

16049

AN:

41406

American (AMR)

AF:

0.186

AC:

2836

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1130

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

607

AN:

5166

South Asian (SAS)

AF:

0.195

AC:

943

AN:

4832

European-Finnish (FIN)

AF:

0.108

AC:

1143

AN:

10566

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.150

AC:

10179

AN:

67964

Other (OTH)

AF:

0.223

AC:

471

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1218

2436

3655

4873

6091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.180

Hom.:

10923

Bravo

AF:

0.233

TwinsUK

AF:

0.134

AC:

498

ALSPAC

AF:

0.128

AC:

493

ESP6500AA

AF:

0.374

AC:

1648

ESP6500EA

AF:

0.159

AC:

1367

ExAC

AF:

0.182

AC:

22103

Asia WGS

AF:

0.123

AC:

428

AN:

3478

EpiCase

AF:

0.170

EpiControl

AF:

0.170

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Trichohepatoenteric syndrome 1

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

1.3

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.23

Sift

Benign

0.086

.;T

Sift4G

Benign

0.080

.;T

Polyphen

0.70

P;P

Vest4

0.24

MutPred

0.38

Gain of ubiquitination at K1295 (P = 0.0638);Gain of ubiquitination at K1295 (P = 0.0638);

MPC

0.19

ClinPred

0.022

GERP RS

3.2

Varity_R

0.27

gMVP

0.66

Mutation Taster

=88/12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over