19-31277216-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_020856.4(TSHZ3):c.2577G>A(p.Thr859=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,614,174 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 61 hom. )

Consequence

TSHZ3
NM_020856.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

TSHZ3 (HGNC:30700): (teashirt zinc finger homeobox 3) This gene encodes a zinc-finger transcription factor that regulates smooth muscle cell differentiation in the developing urinary tract. Consistent with this role, mice in which this gene has been inactivated exhibit abnormal gene expression in urinary tract smooth muscle cell precursors and kidney defects including hydronephrosis. The encoded transcription factor comprises a gene silencing complex that inhibits caspase expression. Reduced expression of this gene and consequent caspase upregulation may be correlated with progression of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2016]

TSHZ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 19-31277216-C-T is Benign according to our data. Variant chr19-31277216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.23 with no splicing effect.

BS2

High AC in GnomAd at 730 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TSHZ3	NM_020856.4 linkuse as main transcript	c.2577G>A	p.Thr859=	synonymous_variant	2/2	ENST00000240587.5
TSHZ3	XM_047439132.1 linkuse as main transcript	c.2577G>A	p.Thr859=	synonymous_variant	3/3
TSHZ3	NR_138035.2 linkuse as main transcript	n.258-49076G>A		intron_variant, non_coding_transcript_variant
TSHZ3	NR_138036.2 linkuse as main transcript	n.258-49076G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ3	ENST00000240587.5 linkuse as main transcript	c.2577G>A	p.Thr859=	synonymous_variant	2/2	1	NM_020856.4	P1
TSHZ3	ENST00000651361.1 linkuse as main transcript	n.64-34341G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

730

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00727

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00580

AC:

1459

AN:

251478

Hom.:

AF XY:

0.00632

AC XY:

859

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00820

Gnomad FIN exome

AF:

0.0437

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00304

AC:

4438

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2356

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00874

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00479

AC:

730

AN:

152286

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

501

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00727

Gnomad4 FIN

AF:

0.0505

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.000873

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TSHZ3: BP4, BS2 -

TSHZ3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 20, 2021

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

-0.28

Cadd

Benign

Dann

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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