rs4805666

chr19-31286601-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.41-6849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,142 control chromosomes in the GnomAD database, including 7,916 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 0.31 (7916 hom., cov: 33)
• Consequence: TSHZ3 NM_020856.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ3	NM_020856.4	c.41-6849G>A		intron_variant		ENST00000240587.5
TSHZ3	XM_047439132.1	c.41-6849G>A		intron_variant
TSHZ3	NR_138035.2	n.258-58461G>A		intron_variant, non_coding_transcript_variant
TSHZ3	NR_138036.2	n.258-58461G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-6849G>A		intron_variant		1	NM_020856.4	P1
TSHZ3	ENST00000560707.1	n.277-6849G>A		intron_variant, non_coding_transcript_variant		3
TSHZ3	ENST00000651361.1	n.64-43726G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47848 AN: 152024 Hom.: 7898 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.315 AC: 47923 AN: 152142 Hom.: 7916 Cov.: 33 AF XY: 0.314 AC XY: 23348 AN XY: 74384

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.305

Alfa AF: 0.277 Hom.: 3256

Bravo AF: 0.331

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.64
Dann	Benign	0.45

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: rs4805666; hg19: chr19-31777507;