rs3744908

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 327806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-75286049-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ1	NM_001308210.2 link	c.642T>C	p.Tyr214Tyr	synonymous_variant	Exon 2 of 2	ENST00000580243.3	NP_001295139.1	Q6ZSZ6-1
TSHZ1	NM_005786.6 link	c.507T>C	p.Tyr169Tyr	synonymous_variant	Exon 2 of 2		NP_005777.3	Q6ZSZ6-2A7YF73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSHZ1	ENST00000580243.3 link	c.642T>C	p.Tyr214Tyr	synonymous_variant	Exon 2 of 2	2	NM_001308210.2	ENSP00000464391.1	Q6ZSZ6-1
TSHZ1	ENST00000322038.5 link	c.507T>C	p.Tyr169Tyr	synonymous_variant	Exon 2 of 2	1		ENSP00000323584.5	Q6ZSZ6-2
TSHZ1	ENST00000560918.2 link	c.507T>C	p.Tyr169Tyr	synonymous_variant	Exon 2 of 2	4		ENSP00000453834.2	H0YN23
TSHZ1	ENST00000584217.1 link	n.3186T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

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

GnomAD3 exomes

AF:

0.352

AC:

87608

AN:

248922

Hom.:

16406

AF XY:

0.362

AC XY:

48771

AN XY:

134656

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 SAS exome

AF:

0.396

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

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.325

AC:

49421

AN:

151972

Hom.:

8994

Cov.:

AF XY:

0.325

AC XY:

24161

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.368

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.377

Hom.:

8235

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

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

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.073

DANN

Benign

0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over