Genetic Variant TSHZ1:c.-981_-980delAG (chr18-75210894-TGA-T) – 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.-981_-980delAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 88,446 control chromosomes in the GnomAD database, including 653 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.13 ( 653 hom., cov: 14)

Exomes 𝑓: 0.014 ( 0 hom. )

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: 0.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

aural atresia, congenital
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae), ClinGen
congenital vertical talus
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

TSHZ1 links:

Genome browser will be placed here

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 = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308210.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	NM_001308210.2	MANE Select	c.-981_-980delAG		5_prime_UTR	Exon 1 of 2	NP_001295139.1	Q6ZSZ6-1
	TSHZ1	NM_005786.6		c.-443_-442delAG		5_prime_UTR	Exon 1 of 2	NP_005777.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.-981_-980delAG		5_prime_UTR	Exon 1 of 2	ENSP00000464391.1	Q6ZSZ6-1
	TSHZ1	ENST00000322038.5	TSL:1	c.-443_-442delAG		5_prime_UTR	Exon 1 of 2	ENSP00000323584.5	Q6ZSZ6-2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

11437

AN:

88312

Hom.:

655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.00935

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.000766

Gnomad SAS

AF:

0.0645

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.0143

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0179

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.129

AC:

11438

AN:

88376

Hom.:

653

Cov.:

AF XY:

0.123

AC XY:

5278

AN XY:

42760

show subpopulations

African (AFR)

AF:

0.224

AC:

4753

AN:

21206

American (AMR)

AF:

0.137

AC:

1296

AN:

9468

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

467

AN:

2696

East Asian (EAS)

AF:

0.000769

AC:

AN:

2602

South Asian (SAS)

AF:

0.0642

AC:

125

AN:

1946

European-Finnish (FIN)

AF:

0.0179

AC:

103

AN:

5756

Middle Eastern (MID)

AF:

0.313

AC:

AN:

192

European-Non Finnish (NFE)

AF:

0.104

AC:

4422

AN:

42568

Other (OTH)

AF:

0.157

AC:

204

AN:

1300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

431

862

1293

1724

2155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0708

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aural atresia, congenital (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over