18-75285722-C-T

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.315C>T(p.Ser105Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,672 control chromosomes in the GnomAD database, including 69,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5142 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64811 hom. )

Consequence

TSHZ1
NM_001308210.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.370

Publications

19 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=-0.73).

BP6

Variant 18-75285722-C-T is Benign according to our data. Variant chr18-75285722-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ1	NM_001308210.2 link	c.315C>T	p.Ser105Ser	synonymous_variant	Exon 2 of 2	ENST00000580243.3	NP_001295139.1	Q6ZSZ6-1
TSHZ1	NM_005786.6 link	c.180C>T	p.Ser60Ser	synonymous_variant	Exon 2 of 2		NP_005777.3	Q6ZSZ6-2A7YF73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3 link	c.315C>T	p.Ser105Ser	synonymous_variant	Exon 2 of 2	2	NM_001308210.2	ENSP00000464391.1		Q6ZSZ6-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35861

AN:

151948

Hom.:

5144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.263

AC:

65894

AN:

250932

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.0703

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.293

AC:

427570

AN:

1461606

Hom.:

64811

Cov.:

AF XY:

0.291

AC XY:

211507

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.0642

AC:

2148

AN:

33480

American (AMR)

AF:

0.253

AC:

11311

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7806

AN:

26126

East Asian (EAS)

AF:

0.165

AC:

6562

AN:

39698

South Asian (SAS)

AF:

0.210

AC:

18114

AN:

86242

European-Finnish (FIN)

AF:

0.299

AC:

15942

AN:

53390

Middle Eastern (MID)

AF:

0.275

AC:

1583

AN:

5766

European-Non Finnish (NFE)

AF:

0.313

AC:

347566

AN:

1111818

Other (OTH)

AF:

0.274

AC:

16538

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

18175

36350

54524

72699

90874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10998

21996

32994

43992

54990

<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:

0.236

AC:

35852

AN:

152066

Hom.:

5142

Cov.:

AF XY:

0.236

AC XY:

17556

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0734

AC:

3049

AN:

41514

American (AMR)

AF:

0.299

AC:

4570

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1048

AN:

3472

East Asian (EAS)

AF:

0.149

AC:

770

AN:

5162

South Asian (SAS)

AF:

0.196

AC:

944

AN:

4814

European-Finnish (FIN)

AF:

0.286

AC:

3018

AN:

10562

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.318

AC:

21607

AN:

67940

Other (OTH)

AF:

0.248

AC:

524

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1337

2675

4012

5350

6687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.292

Hom.:

25389

Bravo

AF:

0.228

Asia WGS

AF:

0.195

AC:

679

AN:

3478

EpiCase

AF:

0.325

EpiControl

AF:

0.327

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.5

(source)

DANN

Benign

0.63

PhyloP100

0.37

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over