Variant 11-118530902-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000302783.10(TTC36):c.556C>T(p.Arg186Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,503,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TTC36
ENST00000302783.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.72

Variant links:

Genes affected

TTC36 (HGNC:33708): (tetratricopeptide repeat domain 36) The protein encoded by this gene has three tetratricopeptide repeats and is a chaperone for heat shock protein 70. The encoded protein may function as a tumor suppressor in hepatocellular carcinoma (HCC) since it promotes apoptosis but is downregulated in HCC. [provided by RefSeq, Sep 2016]

TTC36 links:

TTC36-AS1 (HGNC:):

TTC36-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03991556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC36	NM_001080441.4 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	3/3	ENST00000302783.10	NP_001073910.1	A6NLP5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC36	ENST00000302783.10 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	3/3	1	NM_001080441.4	ENSP00000307640.4		A6NLP5-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000888

AC:

AN:

1350972

Hom.:

Cov.:

AF XY:

0.00000600

AC XY:

AN XY:

666380

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000306

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.39e-7

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000132

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.556C>T (p.R186C) alteration is located in exon 3 (coding exon 3) of the TTC36 gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.9

DANN

Benign

0.93

DEOGEN2

Benign

0.016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.60

M_CAP

Benign

0.044

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

REVEL

Benign

0.039

Sift

Benign

0.078

Sift4G

Benign

0.071

Polyphen

0.0

Vest4

0.074

MutPred

0.32

Loss of MoRF binding (P = 0.0021);

MVP

0.082

MPC

0.38

ClinPred

0.088

GERP RS

-9.5

Varity_R

0.075

gMVP

0.30

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