19-31298019-C-A

Position:

• chr19-31298019-C-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TSHZ3	NM_020856.4	c.41-18267G>T		intron_variant		ENST00000240587.5	NP_065907.2
TSHZ3	XM_047439132.1	c.41-18267G>T		intron_variant			XP_047295088.1
TSHZ3	NR_138035.2	n.257+51161G>T		intron_variant
TSHZ3	NR_138036.2	n.257+51161G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-18267G>T		intron_variant		1	NM_020856.4	ENSP00000240587.4
TSHZ3	ENST00000560707.1	n.276+7469G>T		intron_variant		3
TSHZ3	ENST00000651361.1	n.63+51161G>T		intron_variant

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

Gnomad4 AFR AF: 0.958

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.829

Alfa AF: 0.790 Hom.: 24806

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

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: rs7255674; hg19: chr19-31788925;