rs17581484

chr19-31292593-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TSHZ3	NM_020856.4	c.41-12841G>A		intron_variant		ENST00000240587.5
TSHZ3	XM_047439132.1	c.41-12841G>A		intron_variant
TSHZ3	NR_138035.2	n.257+56587G>A		intron_variant, non_coding_transcript_variant
TSHZ3	NR_138036.2	n.257+56587G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-12841G>A		intron_variant		1	NM_020856.4	P1
TSHZ3	ENST00000560707.1	n.277-12841G>A		intron_variant, non_coding_transcript_variant		3
TSHZ3	ENST00000651361.1	n.64-49718G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0477

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00540

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0498

Alfa AF: 0.0763 Hom.: 73

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

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

Other links and lift over

dbSNP: rs17581484; hg19: chr19-31783499;