Variant 12-109908922-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001143852.2(TCHP):c.864G>T(p.Gln288His) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,614,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TCHP
NM_001143852.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCHP	NM_001143852.2 linkuse as main transcript	c.864G>T	p.Gln288His	missense_variant	8/13	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.864G>T	p.Gln288His	missense_variant	8/13	1	NM_001143852.2	ENSP00000384520	P1
TCHP	ENST00000312777.9 linkuse as main transcript	c.864G>T	p.Gln288His	missense_variant	8/13	1		ENSP00000324404	P1
TCHP	ENST00000549550.1 linkuse as main transcript	n.108G>T		non_coding_transcript_exon_variant	1/4	3
TCHP	ENST00000544838.5 linkuse as main transcript	c.864G>T	p.Gln288His	missense_variant, NMD_transcript_variant	8/15	2		ENSP00000440838

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152226

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:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251354

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

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

Aug 30, 2021

The c.864G>T (p.Q288H) alteration is located in exon 8 (coding exon 7) of the TCHP gene. This alteration results from a G to T substitution at nucleotide position 864, causing the glutamine (Q) at amino acid position 288 to be replaced by a histidine (H). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.9

M;M

MutationTaster

Benign

0.69

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.65

MutPred

0.19

Gain of catalytic residue at R285 (P = 0.0843);Gain of catalytic residue at R285 (P = 0.0843);

MVP

0.47

MPC

0.39

ClinPred

0.79

GERP RS

4.5

Varity_R

0.49

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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