Variant chr19-31349174-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_020856.4(TSHZ3):c.40+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,541,492 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

TSHZ3
NM_020856.4 splice_region, intron

Scores

Splicing: ADA: 0.0002968

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0460

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-AS1 (HGNC:):

TSHZ3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-31349174-T-C is Benign according to our data. Variant chr19-31349174-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3053314.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 69 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ3	NM_020856.4 linkuse as main transcript	c.40+6A>G		splice_region_variant, intron_variant		ENST00000240587.5	NP_065907.2	Q63HK5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TSHZ3	ENST00000240587.5 linkuse as main transcript	c.40+6A>G	splice_region_variant, intron_variant	1	NM_020856.4	ENSP00000240587.4	Q63HK5
TSHZ3	ENST00000558569.1 linkuse as main transcript	c.40+6A>G	splice_region_variant, intron_variant	2		ENSP00000475613.1	U3KQ78
TSHZ3-AS1	ENST00000585336.1 linkuse as main transcript	n.37+257T>C	intron_variant	4
TSHZ3	ENST00000651361.1 linkuse as main transcript	n.63+6A>G	splice_region_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000456

AC:

AN:

151456

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

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:

0.000634

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000315

AC:

AN:

139828

Hom.:

AF XY:

0.000318

AC XY:

AN XY:

75368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000501

Gnomad ASJ exome

AF:

0.000123

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000570

Gnomad OTH exome

AF:

0.000245

GnomAD4 exome

AF:

0.000348

AC:

483

AN:

1389924

Hom.:

Cov.:

AF XY:

0.000334

AC XY:

229

AN XY:

685746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000595

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000410

Gnomad4 OTH exome

AF:

0.000329

GnomAD4 genome

AF:

0.000455

AC:

AN:

151568

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000634

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000547

Hom.:

Bravo

AF:

0.000404

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TSHZ3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 24, 2020

This variant is classified as likely 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

-0.51

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00030

dbscSNV1_RF

Benign

0.028

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