rs112669427

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001308210.2(TSHZ1):c.503C>T(p.Thr168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,519,166 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 11 hom., cov: 23)

Exomes 𝑓: 0.0017 ( 15 hom. )

Consequence

TSHZ1
NM_001308210.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.06

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029379427).

BP6

Variant 18-75285910-C-T is Benign according to our data. Variant chr18-75285910-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 327802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00769 (1117/145244) while in subpopulation AFR AF = 0.0238 (927/39004). AF 95% confidence interval is 0.0225. There are 11 homozygotes in GnomAd4. There are 534 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High AC in GnomAd4 at 1117 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.503C>T	p.Thr168Ile	missense	Exon 2 of 2	NP_001295139.1	Q6ZSZ6-1
	TSHZ1	NM_005786.6		c.368C>T	p.Thr123Ile	missense	Exon 2 of 2	NP_005777.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.503C>T	p.Thr168Ile	missense	Exon 2 of 2	ENSP00000464391.1	Q6ZSZ6-1
TSHZ1	ENST00000322038.5	TSL:1	c.368C>T	p.Thr123Ile	missense	Exon 2 of 2	ENSP00000323584.5	Q6ZSZ6-2
TSHZ1	ENST00000560918.2	TSL:4	c.368C>T	p.Thr123Ile	missense	Exon 2 of 2	ENSP00000453834.2	H0YN23

Frequencies

GnomAD3 genomes

AF:

0.00768

AC:

1115

AN:

145134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00558

Gnomad ASJ

AF:

0.00504

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000452

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.0129

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00866

GnomAD2 exomes

AF:

0.00313

AC:

469

AN:

150066

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00363

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00577

GnomAD4 exome

AF:

0.00171

AC:

2350

AN:

1373922

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1091

AN XY:

677780

show subpopulations

African (AFR)

AF:

0.0257

AC:

802

AN:

31232

American (AMR)

AF:

0.00404

AC:

144

AN:

35656

Ashkenazi Jewish (ASJ)

AF:

0.00428

AC:

106

AN:

24788

East Asian (EAS)

AF:

0.00

AC:

AN:

35358

South Asian (SAS)

AF:

0.000700

AC:

AN:

78536

European-Finnish (FIN)

AF:

0.0000216

AC:

AN:

46218

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5060

European-Non Finnish (NFE)

AF:

0.000884

AC:

937

AN:

1060150

Other (OTH)

AF:

0.00436

AC:

248

AN:

56924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

135

270

406

541

676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.00769

AC:

1117

AN:

145244

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

534

AN XY:

70612

show subpopulations

African (AFR)

AF:

0.0238

AC:

927

AN:

39004

American (AMR)

AF:

0.00557

AC:

AN:

14350

Ashkenazi Jewish (ASJ)

AF:

0.00504

AC:

AN:

3372

East Asian (EAS)

AF:

0.00

AC:

AN:

4904

South Asian (SAS)

AF:

0.000452

AC:

AN:

4428

European-Finnish (FIN)

AF:

0.000200

AC:

AN:

9978

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

66034

Other (OTH)

AF:

0.00858

AC:

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00400

Hom.:

Bravo

AF:

0.00936

ESP6500AA

AF:

0.0211

AC:

ESP6500EA

AF:

0.000478

AC:

ExAC

AF:

0.00181

AC:

200

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

TSHZ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.13

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.4

PhyloP100

2.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Benign

0.032

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.079

MVP

0.33

MPC

0.41

ClinPred

0.0075

GERP RS

4.2

Varity_R

0.048

gMVP

0.44

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over