18-75210896-A-AG

Position:

• chr18-75210896-A-AG

Variant summary

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

The NM_001308210.2(TSHZ1):​c.-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 0.070 (453 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, multiple submitters, no conflicts U:2
• 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 (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.-970dup		5_prime_UTR_variant	1/2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.-432dup		5_prime_UTR_variant	1/2		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.-970dup		5_prime_UTR_variant	1/2	2	NM_001308210.2	ENSP00000464391	P1
TSHZ1	ENST00000322038.5	c.-432dup		5_prime_UTR_variant	1/2	1		ENSP00000323584

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 5609 AN: 79650 Hom.: 453 Cov.: 0

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0229

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.00962

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0820

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0588

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: 0.0705 AC: 5617 AN: 79730 Hom.: 453 Cov.: 0 AF XY: 0.0681 AC XY: 2574 AN XY: 37780

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.00962

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0580

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Aural atresia, congenital Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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: rs372787732; hg19: chr18-72922851;