chr18-75286488-C-CA

Variant names:

• chr18-75286488-C-CA
• rs730882069
• NM_001308210.2:c.1081_1082insA

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001308210.2(TSHZ1):​c.1081_1082insA​(p.Pro361HisfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSHZ1 NM_001308210.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.69
• Publications: 1 publications found

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]

TSHZ1 Gene-Disease associations (from GenCC):

• aural atresia, congenital

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.665 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-75286488-C-CA is Pathogenic according to our data. Variant chr18-75286488-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 31185.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.1081_1082insA	p.Pro361HisfsTer6	frameshift_variant	Exon 2 of 2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.946_947insA	p.Pro316HisfsTer6	frameshift_variant	Exon 2 of 2		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.1081_1082insA	p.Pro361HisfsTer6	frameshift_variant	Exon 2 of 2	2	NM_001308210.2	ENSP00000464391.1
TSHZ1	ENST00000322038.5	c.946_947insA	p.Pro316HisfsTer6	frameshift_variant	Exon 2 of 2	1		ENSP00000323584.5
TSHZ1	ENST00000584217.1	n.3625_3626insA		non_coding_transcript_exon_variant	Exon 1 of 1	6
TSHZ1	ENST00000560918.2	c.*116_*117insA		downstream_gene_variant		4		ENSP00000453834.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Aural atresia, congenital Pathogenic:1

Mar 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=2/198	disease causing (ClinVar)

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

dbSNP: rs730882069; hg19: chr18-72998443;