chr12-109903141-C-T

Variant names:

• chr12-109903141-C-T
• rs766401453
• NM_001143852.2:c.115C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001143852.2(TCHP):​c.115C>T​(p.Arg39Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TCHP NM_001143852.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.49
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29667002).

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.115C>T	p.Arg39Cys	missense	Exon 2 of 13	NP_001137324.1	Q9BT92
	TCHP	NM_032300.5		c.115C>T	p.Arg39Cys	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.115C>T	p.Arg39Cys	missense	Exon 2 of 13	ENSP00000384520.4	Q9BT92
	TCHP	ENST00000312777.9	TSL:1	c.115C>T	p.Arg39Cys	missense	Exon 2 of 13	ENSP00000324404.5	Q9BT92
	TCHP	ENST00000536408.2	TSL:1	c.115C>T	p.Arg39Cys	missense	Exon 2 of 5	ENSP00000441835.2	F5GWH6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251442 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461688 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111860

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.5
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.54
MutPred		0.33		Gain of catalytic residue at M43 (P = 0.0021)
MVP		0.61
MPC		0.35
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.34
gMVP		0.18
Mutation Taster		=82/18	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: rs766401453; hg19: chr12-110340946; COSMIC: COSV57166647;