chr18-75286049-T-G

Variant names:

• chr18-75286049-T-G
• rs3744908
• NM_001308210.2:c.642T>G

Variant summary

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

The NM_001308210.2(TSHZ1):​c.642T>G​(p.Tyr214*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y214Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSHZ1 NM_001308210.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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 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
TSHZ1	NM_001308210.2	c.642T>G	p.Tyr214*	stop_gained	Exon 2 of 2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.507T>G	p.Tyr169*	stop_gained	Exon 2 of 2		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.642T>G	p.Tyr214*	stop_gained	Exon 2 of 2	2	NM_001308210.2	ENSP00000464391.1
TSHZ1	ENST00000322038.5	c.507T>G	p.Tyr169*	stop_gained	Exon 2 of 2	1		ENSP00000323584.5
TSHZ1	ENST00000560918.2	c.507T>G	p.Tyr169*	stop_gained	Exon 2 of 2	4		ENSP00000453834.2
TSHZ1	ENST00000584217.1	n.3186T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	23
DANN	Benign	0.97
Eigen	Uncertain	0.43
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.34	N
Vest4		0.40
GERP RS		-1.8

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

LitVar

Other links and lift over

dbSNP: rs3744908; hg19: chr18-72998004;