Variant 5-95540824-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014639.4(SKIC3):c.409C>G(p.Arg137Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SKIC3
NM_014639.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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 links:

SKIC3 (HGNC:):

SKIC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08343923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKIC3	NM_014639.4 linkuse as main transcript	c.409C>G	p.Arg137Gly	missense_variant	8/43	ENST00000358746.7	NP_055454.1	Q6PGP7
SKIC3	XM_047417937.1 linkuse as main transcript	c.409C>G	p.Arg137Gly	missense_variant	8/43		XP_047273893.1
SKIC3	XM_047417938.1 linkuse as main transcript	c.409C>G	p.Arg137Gly	missense_variant	8/29		XP_047273894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIC3	ENST00000358746.7 linkuse as main transcript	c.409C>G	p.Arg137Gly	missense_variant	8/43	1	NM_014639.4	ENSP00000351596.3		Q6PGP7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251278

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 03, 2022

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 137 of the TTC37 protein (p.Arg137Gly). This variant is present in population databases (rs776321294, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TTC37-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0040

T;T;T

Eigen

Benign

0.0024

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.2

M;M;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.27

.;T;D

Sift4G

Benign

0.15

.;T;D

Polyphen

0.041

B;B;B

Vest4

0.46

MutPred

0.45

Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);.;

MVP

0.79

MPC

0.16

ClinPred

0.074

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over