rs1078373

Positions:

• chr19-31310224-G-A
• chr19-31310224-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020856.4(TSHZ3):​c.41-30472C>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

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=-0.91).
• 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/exons	MANE	UniProt
TSHZ3	NM_020856.4	c.41-30472C>T		intron_variant		ENST00000240587.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-30472C>T		intron_variant		1	NM_020856.4	P1
TSHZ3	ENST00000558569.1	c.41-1515C>T		intron_variant		2
TSHZ3	ENST00000651361.1	n.63+38956C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.305

Alfa AF: 0.353 Hom.: 23008

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

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: rs1078373; hg19: chr19-31801130;