18-75211003-A-AG

Position:

• chr18-75211003-A-AG

Variant summary

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

The NM_001308210.2(TSHZ1):​c.-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 0.55 (20530 hom., cov: 0)
  • Exomes 𝑓: 0.29 (2 hom.)
• Consequence: TSHZ1 NM_001308210.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.-866dup		5_prime_UTR_variant	1/2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.-328dup		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.-866dup		5_prime_UTR_variant	1/2	2	NM_001308210.2	ENSP00000464391	P1
TSHZ1	ENST00000322038.5	c.-328dup		5_prime_UTR_variant	1/2	1		ENSP00000323584

Frequencies

GnomAD3 genomes AF: 0.554 AC: 75625 AN: 136504 Hom.: 20511 Cov.: 0

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.635

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.292 AC: 7 AN: 24 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.554 AC: 75667 AN: 136568 Hom.: 20530 Cov.: 0 AF XY: 0.552 AC XY: 36273 AN XY: 65718

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.604

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: rs66582660; hg19: chr18-72922958;