chr12-109903031-C-T

Variant names:

• chr12-109903031-C-T
• rs145451565
• NM_001143852.2:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001143852.2(TCHP):​c.5C>T​(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,593,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: TCHP NM_001143852.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143852.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCHP	NM_001143852.2	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 2 of 13	NP_001137324.1	Q9BT92
	TCHP	NM_032300.5		c.5C>T	p.Ala2Val	missense	Exon 2 of 13	NP_115676.1	Q9BT92

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCHP	ENST00000405876.9	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 2 of 13	ENSP00000384520.4	Q9BT92
	TCHP	ENST00000312777.9	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 2 of 13	ENSP00000324404.5	Q9BT92
	TCHP	ENST00000536408.2	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 2 of 5	ENSP00000441835.2	F5GWH6

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000914 AC: 22 AN: 240648 AF XY: 0.0000688

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000182

Gnomad OTH exome AF: 0.000339

GnomAD4 exome AF: 0.000170 AC: 245 AN: 1441586 Hom.: 0 Cov.: 30 AF XY: 0.000158 AC XY: 113 AN XY: 717228

African (AFR) AF: 0.0000305 AC: 1 AN: 32838

American (AMR) AF: 0.0000244 AC: 1 AN: 40916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 39390

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4840

European-Non Finnish (NFE) AF: 0.000214 AC: 236 AN: 1101426

Other (OTH) AF: 0.000101 AC: 6 AN: 59322

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74326

African (AFR) AF: 0.0000966 AC: 4 AN: 41418

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000137 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.63
MVP		0.67
MPC		0.41
ClinPred		0.58	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.080
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs145451565; hg19: chr12-110340836; COSMIC: COSV100452657;