18-75285688-G-T

Position:

• chr18-75285688-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308210.2(TSHZ1):​c.281G>T​(p.Arg94Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSHZ1 NM_001308210.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.97

Genes affected

TSHZ1 (HGNC:10669): (teashirt zinc finger homeobox 1) This gene encodes a colon cancer antigen that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type zinc-finger protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene may be associated with congenital aural atresia syndrome. [provided by RefSeq, Jan 2012]

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=0.08482835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.281G>T	p.Arg94Leu	missense_variant	2/2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.146G>T	p.Arg49Leu	missense_variant	2/2		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.281G>T	p.Arg94Leu	missense_variant	2/2	2	NM_001308210.2	ENSP00000464391	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

TSHZ1-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 2024

The TSHZ1 c.146G>T variant is predicted to result in the amino acid substitution p.Arg49Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.15	.;T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.89
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.085	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;.;.
MutationTaster	Benign	0.53	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N;.;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;.;D;D
Sift4G	Uncertain	0.039	D;D;T;D
Polyphen		0.094	.;B;.;.
Vest4		0.19
MutPred		0.15		.;Loss of loop (P = 0.0512);.;.;
MVP		0.38
MPC		0.41
ClinPred		0.59	D
GERP RS		0.36
Varity_R		0.16
gMVP		0.17

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: chr18-72997643; COSMIC: COSV59015627;