19-31298019-C-A

Variant names:

• chr19-31298019-C-A
• rs7255674
• NM_020856.4:c.41-18267G>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.41-18267G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,102 control chromosomes in the GnomAD database, including 53,916 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 0.84 (53916 hom., cov: 31)
• Consequence: TSHZ3 NM_020856.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ3	NM_020856.4	c.41-18267G>T		intron_variant	Intron 1 of 1	ENST00000240587.5	NP_065907.2
TSHZ3	NR_138035.2	n.257+51161G>T		intron_variant	Intron 1 of 3
TSHZ3	NR_138036.2	n.257+51161G>T		intron_variant	Intron 1 of 4
TSHZ3	XM_047439132.1	c.41-18267G>T		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.41-18267G>T		intron_variant	Intron 1 of 1	1	NM_020856.4	ENSP00000240587.4
TSHZ3	ENST00000560707.1	n.276+7469G>T		intron_variant	Intron 1 of 1	3
TSHZ3	ENST00000651361.1	n.63+51161G>T		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127134 AN: 151984 Hom.: 53859 Cov.: 31

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.837 AC: 127249 AN: 152102 Hom.: 53916 Cov.: 31 AF XY: 0.834 AC XY: 61961 AN XY: 74326

African (AFR) AF: 0.958 AC: 39758 AN: 41506

American (AMR) AF: 0.825 AC: 12619 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2816 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5060 AN: 5152

South Asian (SAS) AF: 0.914 AC: 4402 AN: 4816

European-Finnish (FIN) AF: 0.668 AC: 7064 AN: 10570

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52782 AN: 67980

Other (OTH) AF: 0.829 AC: 1752 AN: 2114

Alfa AF: 0.799 Hom.: 35911

Bravo AF: 0.852

Asia WGS AF: 0.944 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.031
DANN	Benign	0.56
PhyloP100		-2.0
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: rs7255674; hg19: chr19-31788925;