12-109911099-A-G

Position:

• chr12-109911099-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCHP	NM_001143852.2	c.916A>G	p.Lys306Glu	missense_variant	9/13	ENST00000405876.9	NP_001137324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCHP	ENST00000405876.9	c.916A>G	p.Lys306Glu	missense_variant	9/13	1	NM_001143852.2	ENSP00000384520	P1
TCHP	ENST00000312777.9	c.916A>G	p.Lys306Glu	missense_variant	9/13	1		ENSP00000324404	P1
TCHP	ENST00000549550.1	n.160A>G		non_coding_transcript_exon_variant	2/4	3
TCHP	ENST00000544838.5	c.916A>G	p.Lys306Glu	missense_variant, NMD_transcript_variant	9/15	2		ENSP00000440838

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.916A>G (p.K306E) alteration is located in exon 9 (coding exon 8) of the TCHP gene. This alteration results from a A to G substitution at nucleotide position 916, causing the lysine (K) at amino acid position 306 to be replaced by a glutamic acid (E). 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	0.085
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.76
DEOGEN2	Benign	0.092	T;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;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.95	L;L
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.068
Sift	Benign	0.19	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.010	B;B
Vest4		0.24
MutPred		0.24		Loss of ubiquitination at K306 (P = 0.0023);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-110348904;