Variant 12-109903079-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001143852.2(TCHP):c.53A>G(p.Gln18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

TCHP
NM_001143852.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.984

Variant links:

Genes affected

TCHP (HGNC:28135): (trichoplein keratin filament binding) Involved in apoptotic process; negative regulation of cell growth; and negative regulation of cilium assembly. Located in several cellular components, including apical cortex; cytoskeleton; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TCHP 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=0.06372818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCHP	NM_001143852.2 linkuse as main transcript	c.53A>G	p.Gln18Arg	missense_variant	2/13	ENST00000405876.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCHP	ENST00000405876.9 linkuse as main transcript	c.53A>G	p.Gln18Arg	missense_variant	2/13	1	NM_001143852.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251312

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135854

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1461356

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727012

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000491

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

May 24, 2023

The c.53A>G (p.Q18R) alteration is located in exon 2 (coding exon 1) of the TCHP gene. This alteration results from a A to G substitution at nucleotide position 53, causing the glutamine (Q) at amino acid position 18 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.13

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.0050

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.030

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.37

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.12

MutPred

0.21

Gain of MoRF binding (P = 0.0691);Gain of MoRF binding (P = 0.0691);Gain of MoRF binding (P = 0.0691);

MVP

0.19

MPC

0.14

ClinPred

0.025

GERP RS

3.2

Varity_R

0.019

gMVP

0.034

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