rs17581484

Variant names:

• chr19-31292593-C-T
• rs17581484
• NM_020856.4:c.41-12841G>A

Variant summary

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

The NM_020856.4(TSHZ3):​c.41-12841G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,188 control chromosomes in the GnomAD database, including 421 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 0.066 (421 hom., cov: 32)
• Consequence: TSHZ3 NM_020856.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ3	NM_020856.4	c.41-12841G>A		intron_variant	Intron 1 of 1	ENST00000240587.5	NP_065907.2
TSHZ3	NR_138035.2	n.257+56587G>A		intron_variant	Intron 1 of 3
TSHZ3	NR_138036.2	n.257+56587G>A		intron_variant	Intron 1 of 4
TSHZ3	XM_047439132.1	c.41-12841G>A		intron_variant	Intron 2 of 2		XP_047295088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-12841G>A		intron_variant	Intron 1 of 1	1	NM_020856.4	ENSP00000240587.4
TSHZ3	ENST00000560707.1	n.277-12841G>A		intron_variant	Intron 1 of 1	3
TSHZ3	ENST00000651361.1	n.64-49718G>A		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9988 AN: 152068 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0656 AC: 9989 AN: 152188 Hom.: 421 Cov.: 32 AF XY: 0.0642 AC XY: 4778 AN XY: 74400

African (AFR) AF: 0.0201 AC: 836 AN: 41542

American (AMR) AF: 0.0477 AC: 728 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3468

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5182

South Asian (SAS) AF: 0.0857 AC: 413 AN: 4820

European-Finnish (FIN) AF: 0.0647 AC: 686 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7078 AN: 67988

Other (OTH) AF: 0.0498 AC: 105 AN: 2108

Alfa AF: 0.0750 Hom.: 155

Bravo AF: 0.0607

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.94
PhyloP100		-0.30
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: rs17581484; hg19: chr19-31783499;