Variant 19-31349198-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020856.4(TSHZ3):c.22G>A(p.Ala8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000259 in 1,542,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TSHZ3
NM_020856.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.47

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:

TSHZ3 (HGNC:):

TSHZ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06628123).

BS2

High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ3	NM_020856.4 linkuse as main transcript	c.22G>A	p.Ala8Thr	missense_variant	1/2	ENST00000240587.5	NP_065907.2	Q63HK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSHZ3	ENST00000240587.5 linkuse as main transcript	c.22G>A	p.Ala8Thr	missense_variant	1/2	1	NM_020856.4	ENSP00000240587.4	Q63HK5
TSHZ3	ENST00000558569.1 linkuse as main transcript	c.22G>A	p.Ala8Thr	missense_variant	1/2	2		ENSP00000475613.1	U3KQ78
TSHZ3	ENST00000651361.1 linkuse as main transcript	n.45G>A		non_coding_transcript_exon_variant	1/7
TSHZ3-AS1	ENST00000585336.1 linkuse as main transcript	n.37+281C>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

139714

Hom.:

AF XY:

0.0000398

AC XY:

AN XY:

75382

show subpopulations

Gnomad AFR exome

AF:

0.000630

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1390106

Hom.:

Cov.:

AF XY:

0.00000729

AC XY:

AN XY:

685828

show subpopulations

Gnomad4 AFR exome

AF:

0.000423

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000218

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.0000520

GnomAD4 genome

AF:

0.000138

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.000508

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000935

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000105

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.22G>A (p.A8T) alteration is located in exon 1 (coding exon 1) of the TSHZ3 gene. This alteration results from a G to A substitution at nucleotide position 22, causing the alanine (A) at amino acid position 8 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.93

N;.

REVEL

Benign

0.13

Sift

Uncertain

0.011

D;.

Sift4G

Benign

0.12

T;.

Polyphen

0.98

D;.

Vest4

0.34

MVP

0.37

MPC

0.31

ClinPred

0.16

GERP RS

3.8

Varity_R

0.22

gMVP

0.44

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