18-75210894-TGAG-T

Position:

• chr18-75210894-TGAG-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001308210.2(TSHZ1):​c.-981_-979del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 88,502 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 0)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: TSHZ1 NM_001308210.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00

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 -4 ACMG points.

• BS2: High AC in GnomAd4 at 335 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.-981_-979del		5_prime_UTR_variant	1/2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.-443_-441del		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.-981_-979del		5_prime_UTR_variant	1/2	2	NM_001308210.2	ENSP00000464391	P1
TSHZ1	ENST00000322038.5	c.-443_-441del		5_prime_UTR_variant	1/2	1		ENSP00000323584

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 333 AN: 88368 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00339

Gnomad ASJ AF: 0.00889

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00485

Gnomad NFE AF: 0.000751

Gnomad OTH AF: 0.00544

GnomAD4 exome AF: 0.0143 AC: 1 AN: 70 Hom.: 0 AF XY: 0.0192 AC XY: 1 AN XY: 52

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00379 AC: 335 AN: 88432 Hom.: 3 Cov.: 0 AF XY: 0.00320 AC XY: 137 AN XY: 42784

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.00338

Gnomad4 ASJ AF: 0.00889

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000751

Gnomad4 OTH AF: 0.00538

Alfa AF: 0.00162 Hom.: 2

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

- -

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: rs886054104; hg19: chr18-72922849;