18-75286049-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001308210.2(TSHZ1):c.642T>C(p.Tyr214Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,612,406 control chromosomes in the GnomAD database, including 120,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8994 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111095 hom. )

Consequence

TSHZ1
NM_001308210.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.910

Publications

16 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 18-75286049-T-C is Benign according to our data. Variant chr18-75286049-T-C is described in ClinVar as Benign. ClinVar VariationId is 327806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	NM_001308210.2	MANE Select	c.642T>C	p.Tyr214Tyr	synonymous	Exon 2 of 2	NP_001295139.1
	TSHZ1	NM_005786.6		c.507T>C	p.Tyr169Tyr	synonymous	Exon 2 of 2	NP_005777.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.642T>C	p.Tyr214Tyr	synonymous	Exon 2 of 2	ENSP00000464391.1
TSHZ1	ENST00000322038.5	TSL:1	c.507T>C	p.Tyr169Tyr	synonymous	Exon 2 of 2	ENSP00000323584.5
TSHZ1	ENST00000560918.2	TSL:4	c.507T>C	p.Tyr169Tyr	synonymous	Exon 2 of 2	ENSP00000453834.2

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49409

AN:

151854

Hom.:

8995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.345

GnomAD2 exomes

AF:

0.352

AC:

87608

AN:

248922

AF XY:

0.362

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.386

AC:

563455

AN:

1460434

Hom.:

111095

Cov.:

AF XY:

0.387

AC XY:

281307

AN XY:

726400

show subpopulations

African (AFR)

AF:

0.163

AC:

5453

AN:

33466

American (AMR)

AF:

0.294

AC:

13109

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

10535

AN:

26104

East Asian (EAS)

AF:

0.182

AC:

7205

AN:

39678

South Asian (SAS)

AF:

0.397

AC:

34187

AN:

86126

European-Finnish (FIN)

AF:

0.385

AC:

20397

AN:

52972

Middle Eastern (MID)

AF:

0.398

AC:

2295

AN:

5766

European-Non Finnish (NFE)

AF:

0.403

AC:

447713

AN:

1111364

Other (OTH)

AF:

0.374

AC:

22561

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

22520

45040

67561

90081

112601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13592

27184

40776

54368

67960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.325

AC:

49421

AN:

151972

Hom.:

8994

Cov.:

AF XY:

0.325

AC XY:

24161

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.171

AC:

7102

AN:

41448

American (AMR)

AF:

0.355

AC:

5421

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1424

AN:

3470

East Asian (EAS)

AF:

0.168

AC:

865

AN:

5160

South Asian (SAS)

AF:

0.387

AC:

1860

AN:

4812

European-Finnish (FIN)

AF:

0.368

AC:

3880

AN:

10556

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27729

AN:

67934

Other (OTH)

AF:

0.350

AC:

739

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1614

3228

4842

6456

8070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.371

Hom.:

10718

Bravo

AF:

0.312

Asia WGS

AF:

0.320

AC:

1114

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Aural atresia, congenital

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

TSHZ1-related disorder

Benign:1

Mar 15, 2023

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.073

(source)

DANN

Benign

0.25

PhyloP100

-0.91

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over