19-31310224-G-A

Variant names:

• chr19-31310224-G-A
• rs1078373
• NM_020856.4:c.41-30472C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020856.4(TSHZ3):​c.41-30472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,954 control chromosomes in the GnomAD database, including 7,795 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7795 hom., cov: 31)
• Consequence: TSHZ3 NM_020856.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ3	NM_020856.4	c.41-30472C>T		intron_variant	Intron 1 of 1	ENST00000240587.5	NP_065907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-30472C>T		intron_variant	Intron 1 of 1	1	NM_020856.4	ENSP00000240587.4
TSHZ3	ENST00000558569.1	c.41-1515C>T		intron_variant	Intron 1 of 1	2		ENSP00000475613.1
TSHZ3	ENST00000651361.1	n.63+38956C>T		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46190 AN: 151836 Hom.: 7793 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46194 AN: 151954 Hom.: 7795 Cov.: 31 AF XY: 0.305 AC XY: 22679 AN XY: 74256

African (AFR) AF: 0.155 AC: 6435 AN: 41480

American (AMR) AF: 0.282 AC: 4303 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3466

East Asian (EAS) AF: 0.453 AC: 2319 AN: 5124

South Asian (SAS) AF: 0.386 AC: 1856 AN: 4806

European-Finnish (FIN) AF: 0.367 AC: 3873 AN: 10554

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25386 AN: 67942

Other (OTH) AF: 0.305 AC: 643 AN: 2110

Alfa AF: 0.346 Hom.: 43855

Bravo AF: 0.288

Asia WGS AF: 0.365 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.054
DANN	Benign	0.51
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1078373; hg19: chr19-31801130;