18-75210896-A-AGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001308210.2(TSHZ1):c.-971_-970dup 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 0.18 (1279 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: -0.415

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ1	NM_001308210.2	c.-971_-970dup		5_prime_UTR_variant	1/2	ENST00000580243.3
TSHZ1	NM_005786.6	c.-433_-432dup		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ1	ENST00000580243.3	c.-971_-970dup		5_prime_UTR_variant	1/2	2	NM_001308210.2	P1
TSHZ1	ENST00000322038.5	c.-433_-432dup		5_prime_UTR_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 13734 AN: 78250 Hom.: 1278 Cov.: 0

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.149

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.175 AC: 13743 AN: 78332 Hom.: 1279 Cov.: 0 AF XY: 0.168 AC XY: 6255 AN XY: 37144

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.148

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: rs372787732; hg19: chr18-72922851;