Variant chr18-75285722-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001308210.2(TSHZ1):c.315C>T(p.Ser105=) 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1260276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-75285722-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
TSHZ1	NM_001308210.2 linkuse as main transcript	c.315C>T	p.Ser105=	synonymous_variant	2/2	ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6 linkuse as main transcript	c.180C>T	p.Ser60=	synonymous_variant	2/2		NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3 linkuse as main transcript	c.315C>T	p.Ser105=	synonymous_variant	2/2	2	NM_001308210.2	ENSP00000464391	P1	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

GnomAD3 exomes

AF:

0.263

AC:

65894

AN:

250932

Hom.:

9387

AF XY:

0.266

AC XY:

36146

AN XY:

135636

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 SAS exome

AF:

0.206

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

Gnomad4 AFR exome

AF:

0.0642

Gnomad4 AMR exome

AF:

0.253

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.236

AC:

35852

AN:

152066

Hom.:

5142

Cov.:

AF XY:

0.236

AC XY:

17556

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0734

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.303

Hom.:

18476

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2020	- -

TSHZ1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2023

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

DANN

Benign

0.63

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