rs4805666

Variant names:

• chr19-31286601-C-T
• rs4805666
• NM_020856.4:c.41-6849G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020856.4(TSHZ3):​c.41-6849G>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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
TSHZ3	NM_020856.4	c.41-6849G>A		intron_variant	Intron 1 of 1	ENST00000240587.5	NP_065907.2
TSHZ3	NR_138035.2	n.258-58461G>A		intron_variant	Intron 1 of 3
TSHZ3	NR_138036.2	n.258-58461G>A		intron_variant	Intron 1 of 4
TSHZ3	XM_047439132.1	c.41-6849G>A		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.41-6849G>A		intron_variant	Intron 1 of 1	1	NM_020856.4	ENSP00000240587.4
TSHZ3	ENST00000560707.1	n.277-6849G>A		intron_variant	Intron 1 of 1	3
TSHZ3	ENST00000651361.1	n.64-43726G>A		intron_variant	Intron 1 of 6

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

African (AFR) AF: 0.397 AC: 16467 AN: 41490

American (AMR) AF: 0.392 AC: 6000 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3466

East Asian (EAS) AF: 0.374 AC: 1935 AN: 5168

South Asian (SAS) AF: 0.359 AC: 1731 AN: 4818

European-Finnish (FIN) AF: 0.196 AC: 2081 AN: 10600

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18125 AN: 67994

Other (OTH) AF: 0.305 AC: 643 AN: 2108

Alfa AF: 0.277 Hom.: 4408

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
PhyloP100		-0.47
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: rs4805666; hg19: chr19-31777507;