Genetic Variant TSHZ1:c.-970dupG (chr18-75210896-A-AG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001308210.2(TSHZ1):c.-970dupG 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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.415

Variant links:

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]

TSHZ1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TSHZ1	NM_001308210.2 link	c.-970dupG		5_prime_UTR_variant	Exon 1 of 2	ENST00000580243.3	NP_001295139.1	Q6ZSZ6-1
TSHZ1	NM_005786.6 link	c.-432dupG		5_prime_UTR_variant	Exon 1 of 2		NP_005777.3	Q6ZSZ6-2A7YF73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243 link	c.-970dupG		5_prime_UTR_variant	Exon 1 of 2	2	NM_001308210.2	ENSP00000464391.1		Q6ZSZ6-1
TSHZ1	ENST00000322038 link	c.-432dupG		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000323584.5		Q6ZSZ6-2

Frequencies

GnomAD3 genomes

AF:

0.0704

AC:

5609

AN:

79650

Hom.:

453

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

Gnomad4 Remaining exome

AC:

AN:

GnomAD4 genome

AF:

0.0705

AC:

5617

AN:

79730

Hom.:

453

Cov.:

AF XY:

0.0681

AC XY:

2574

AN XY:

37780

show subpopulations

Gnomad4 AFR

AF:

0.191

AC:

0.19063

AN:

0.19063

Gnomad4 AMR

AF:

0.0420

AC:

0.0419655

AN:

0.0419655

Gnomad4 ASJ

AF:

0.00962

AC:

0.00961538

AN:

0.00961538

Gnomad4 EAS

AF:

0.119

AC:

0.119121

AN:

0.119121

Gnomad4 SAS

AF:

0.0410

AC:

0.0410256

AN:

0.0410256

Gnomad4 FIN

AF:

0.0127

AC:

0.0127097

AN:

0.0127097

Gnomad4 NFE

AF:

0.0205

AC:

0.020542

AN:

0.020542

Gnomad4 OTH

AF:

0.0580

AC:

0.0579568

AN:

0.0579568

Heterozygous variant carriers

183

367

550

734

917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Aural atresia, congenital

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=300/0

polymorphism (auto)

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over