chr12-109911099-A-G

Variant names:

• chr12-109911099-A-G
• NM_001143852.2:c.916A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143852.2(TCHP):​c.916A>G​(p.Lys306Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCHP NM_001143852.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070091635).

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.916A>G	p.Lys306Glu	missense	Exon 9 of 13	NP_001137324.1	Q9BT92
	TCHP	NM_032300.5		c.916A>G	p.Lys306Glu	missense	Exon 9 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.916A>G	p.Lys306Glu	missense	Exon 9 of 13	ENSP00000384520.4	Q9BT92
	TCHP	ENST00000312777.9	TSL:1	c.916A>G	p.Lys306Glu	missense	Exon 9 of 13	ENSP00000324404.5	Q9BT92
	TCHP	ENST00000900220.1		c.892A>G	p.Lys298Glu	missense	Exon 9 of 13	ENSP00000570279.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.085
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.76
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.95	L
PhyloP100		2.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.068
Sift	Benign	0.19	T
Sift4G	Benign	0.11	T
Polyphen		0.010	B
Vest4		0.24
MutPred		0.24		Loss of ubiquitination at K306 (P = 0.0023)
MVP		0.099
MPC		0.10
ClinPred		0.21	T
GERP RS		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.12
Mutation Taster		=88/12	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

hg19: chr12-110348904;