Variant 12-109911202-G-A 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.1019G>A(p.Arg340Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000877 in 1,585,352 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: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

TCHP
NM_001143852.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.627

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=0.020978332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCHP	NM_001143852.2 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant	9/13	ENST00000405876.9	NP_001137324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TCHP	ENST00000405876.9 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant	9/13	1	NM_001143852.2	ENSP00000384520	P1
TCHP	ENST00000312777.9 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant	9/13	1		ENSP00000324404	P1
TCHP	ENST00000549550.1 linkuse as main transcript	n.263G>A		non_coding_transcript_exon_variant	2/4	3
TCHP	ENST00000544838.5 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant, NMD_transcript_variant	9/15	2		ENSP00000440838

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000121

AC:

AN:

207462

Hom.:

AF XY:

0.0000714

AC XY:

AN XY:

112112

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.000105

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.0000648

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000663

AC:

AN:

1433052

Hom.:

Cov.:

AF XY:

0.0000704

AC XY:

AN XY:

710304

show subpopulations

Gnomad4 AFR exome

AF:

0.000756

Gnomad4 AMR exome

AF:

0.0000749

Gnomad4 ASJ exome

AF:

0.0000394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000489

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000527

Gnomad4 OTH exome

AF:

0.0000675

GnomAD4 genome

AF:

0.000289

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000939

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000279

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000116

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 06, 2022

The c.1019G>A (p.R340Q) alteration is located in exon 9 (coding exon 8) of the TCHP gene. This alteration results from a G to A substitution at nucleotide position 1019, causing the arginine (R) at amino acid position 340 to be replaced by a glutamine (Q). 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

0.083

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.058

Sift

Benign

0.11

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.43

B;B

Vest4

0.23

MVP

0.27

MPC

0.10

ClinPred

0.019

GERP RS

-0.79

Varity_R

0.048

gMVP

0.056

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