chr12-109908697-G-A

Variant names:

• chr12-109908697-G-A
• rs923890718
• NM_001143852.2:c.811G>A

Variant summary

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

The NM_001143852.2(TCHP):​c.811G>A​(p.Gly271Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCHP NM_001143852.2 missense, splice_region
• Scores: Splicing: ADA: 0.9570
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.37

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCHP	NM_001143852.2	c.811G>A	p.Gly271Arg	missense_variant, splice_region_variant	Exon 7 of 13	ENST00000405876.9	NP_001137324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCHP	ENST00000405876.9	c.811G>A	p.Gly271Arg	missense_variant, splice_region_variant	Exon 7 of 13	1	NM_001143852.2	ENSP00000384520.4
TCHP	ENST00000312777.9	c.811G>A	p.Gly271Arg	missense_variant, splice_region_variant	Exon 7 of 13	1		ENSP00000324404.5
TCHP	ENST00000544838.5	n.811G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 15	2		ENSP00000440838.1
TCHP	ENST00000549550.1	n.-118G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.13
Sift	Benign	0.049	D;D
Sift4G	Benign	0.77	T;T
Polyphen		0.98	D;D
Vest4		0.62
MutPred		0.23		Gain of methylation at K267 (P = 0.1973);Gain of methylation at K267 (P = 0.1973);
MVP		0.53
MPC		0.42
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.96
dbscSNV1_RF	Benign	0.63
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

LitVar

Other links and lift over

dbSNP: rs923890718; hg19: chr12-110346502;