Genetic Variant TSHZ1:c.-981delA (chr18-75210895-GA-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001308210.2(TSHZ1):c.-981delA 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 0.0034 ( 3 hom., cov: 14)

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, single submitter U:1

Conservation

PhyloP100: -1.16

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 316 AD gene.

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.-981delA		5_prime_UTR	Exon 1 of 2	NP_001295139.1	Q6ZSZ6-1
	TSHZ1	NM_005786.6		c.-443delA		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.-981delA		5_prime_UTR	Exon 1 of 2	ENSP00000464391.1	Q6ZSZ6-1
	TSHZ1	ENST00000322038.5	TSL:1	c.-443delA		5_prime_UTR	Exon 1 of 2	ENSP00000323584.5	Q6ZSZ6-2

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

317

AN:

92020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00473

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00101

Gnomad SAS

AF:

0.000684

Gnomad FIN

AF:

0.00157

Gnomad MID

AF:

0.0141

Gnomad NFE

AF:

0.00362

Gnomad OTH

AF:

0.00415

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

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:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00343

AC:

316

AN:

92098

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

139

AN XY:

45606

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

18168

American (AMR)

AF:

0.00471

AC:

AN:

9546

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

2122

East Asian (EAS)

AF:

0.00102

AC:

AN:

3930

South Asian (SAS)

AF:

0.000684

AC:

AN:

2922

European-Finnish (FIN)

AF:

0.00157

AC:

AN:

8286

Middle Eastern (MID)

AF:

0.00806

AC:

AN:

124

European-Non Finnish (NFE)

AF:

0.00362

AC:

163

AN:

45006

Other (OTH)

AF:

0.00408

AC:

AN:

1226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aural atresia, congenital (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.2

Mutation Taster

=300/0

polymorphism

(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