19-31299416-G-A

Variant names:

• chr19-31299416-G-A
• rs11883254
• NM_020856.4:c.41-19664C>T

Variant summary

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

The ENST00000240587.5(TSHZ3):​c.41-19664C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,156 control chromosomes in the GnomAD database, including 21,703 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 0.51 (21703 hom., cov: 33)
• Consequence: TSHZ3 ENST00000240587.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000240587.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ3	NM_020856.4	MANE Select	c.41-19664C>T		intron	N/A	NP_065907.2
	TSHZ3	NR_138035.2		n.257+49764C>T		intron	N/A
	TSHZ3	NR_138036.2		n.257+49764C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ3	ENST00000240587.5	TSL:1 MANE Select	c.41-19664C>T		intron	N/A	ENSP00000240587.4
	TSHZ3	ENST00000560707.1	TSL:3	n.276+6072C>T		intron	N/A
	TSHZ3	ENST00000651361.1		n.63+49764C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78140 AN: 152038 Hom.: 21670 Cov.: 33

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.514 AC: 78233 AN: 152156 Hom.: 21703 Cov.: 33 AF XY: 0.507 AC XY: 37696 AN XY: 74380

African (AFR) AF: 0.732 AC: 30404 AN: 41518

American (AMR) AF: 0.477 AC: 7295 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1799 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1922 AN: 5164

South Asian (SAS) AF: 0.552 AC: 2658 AN: 4816

European-Finnish (FIN) AF: 0.290 AC: 3071 AN: 10586

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29456 AN: 68000

Other (OTH) AF: 0.517 AC: 1089 AN: 2108

Alfa AF: 0.464 Hom.: 31610

Bravo AF: 0.535

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.066
DANN	Benign	0.65
PhyloP100		-0.21
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: rs11883254; hg19: chr19-31790322;