chr18-75286931-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001308210.2(TSHZ1):c.1524T>C(p.Pro508Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,950 control chromosomes in the GnomAD database, including 125,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11732 hom., cov: 33)

Exomes 𝑓: 0.39 ( 114145 hom. )

Consequence

TSHZ1
NM_001308210.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.29

Publications

17 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-75286931-T-C is Benign according to our data. Variant chr18-75286931-T-C is described in ClinVar as Benign. ClinVar VariationId is 327819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 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.1524T>C	p.Pro508Pro	synonymous	Exon 2 of 2	NP_001295139.1
	TSHZ1	NM_005786.6		c.1389T>C	p.Pro463Pro	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.1524T>C	p.Pro508Pro	synonymous	Exon 2 of 2	ENSP00000464391.1
TSHZ1	ENST00000322038.5	TSL:1	c.1389T>C	p.Pro463Pro	synonymous	Exon 2 of 2	ENSP00000323584.5
TSHZ1	ENST00000584217.1	TSL:6	n.4068T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59146

AN:

151978

Hom.:

11725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.398

GnomAD2 exomes

AF:

0.369

AC:

92604

AN:

250962

AF XY:

0.374

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.393

AC:

573864

AN:

1461856

Hom.:

114145

Cov.:

AF XY:

0.393

AC XY:

285692

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.388

AC:

12995

AN:

33478

American (AMR)

AF:

0.309

AC:

13835

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

10658

AN:

26136

East Asian (EAS)

AF:

0.182

AC:

7214

AN:

39700

South Asian (SAS)

AF:

0.388

AC:

33500

AN:

86258

European-Finnish (FIN)

AF:

0.386

AC:

20591

AN:

53390

Middle Eastern (MID)

AF:

0.414

AC:

2390

AN:

5768

European-Non Finnish (NFE)

AF:

0.404

AC:

449220

AN:

1112006

Other (OTH)

AF:

0.388

AC:

23461

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

24021

48042

72064

96085

120106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13714

27428

41142

54856

68570

<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:

0.389

AC:

59176

AN:

152094

Hom.:

11732

Cov.:

AF XY:

0.386

AC XY:

28732

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.389

AC:

16122

AN:

41496

American (AMR)

AF:

0.386

AC:

5903

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3470

East Asian (EAS)

AF:

0.168

AC:

870

AN:

5164

South Asian (SAS)

AF:

0.379

AC:

1823

AN:

4812

European-Finnish (FIN)

AF:

0.367

AC:

3880

AN:

10572

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.410

AC:

27882

AN:

67982

Other (OTH)

AF:

0.403

AC:

850

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1866

3732

5598

7464

9330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.405

Hom.:

10590

Bravo

AF:

0.385

Asia WGS

AF:

0.328

AC:

1140

AN:

3478

EpiCase

AF:

0.418

EpiControl

AF:

0.421

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0090

(source)

DANN

Benign

0.31

PhyloP100

-3.3

Mutation Taster

=100/0

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

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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