18-75211003-A-AGG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001308210.2(TSHZ1):c.-867_-866dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.011 (24 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSHZ1 NM_001308210.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.987

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1537/136924) while in subpopulation AFR AF= 0.023 (792/34492). AF 95% confidence interval is 0.0216. There are 24 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd at 1521 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ1	NM_001308210.2	c.-867_-866dup		5_prime_UTR_variant	1/2	ENST00000580243.3
TSHZ1	NM_005786.6	c.-329_-328dup		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ1	ENST00000580243.3	c.-867_-866dup		5_prime_UTR_variant	1/2	2	NM_001308210.2	P1
TSHZ1	ENST00000322038.5	c.-329_-328dup		5_prime_UTR_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1521 AN: 136860 Hom.: 24 Cov.: 0

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00326

Gnomad EAS AF: 0.00852

Gnomad SAS AF: 0.00307

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00436

Gnomad OTH AF: 0.0132

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0112 AC: 1537 AN: 136924 Hom.: 24 Cov.: 0 AF XY: 0.0125 AC XY: 821 AN XY: 65900

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00326

Gnomad4 EAS AF: 0.00855

Gnomad4 SAS AF: 0.00308

Gnomad4 FIN AF: 0.0260

Gnomad4 NFE AF: 0.00436

Gnomad4 OTH AF: 0.0141

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aural atresia, congenital Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs66582660; hg19: chr18-72922958;