rs11883254

Positions:

• chr19-31299416-G-A

Variant summary

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

The NM_020856.4(TSHZ3):​c.41-19664C>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 NM_020856.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ3	NM_020856.4	c.41-19664C>T		intron_variant		ENST00000240587.5	NP_065907.2
TSHZ3	XM_047439132.1	c.41-19664C>T		intron_variant			XP_047295088.1
TSHZ3	NR_138035.2	n.257+49764C>T		intron_variant, non_coding_transcript_variant
TSHZ3	NR_138036.2	n.257+49764C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ3	ENST00000240587.5	c.41-19664C>T		intron_variant		1	NM_020856.4	ENSP00000240587	P1
TSHZ3	ENST00000560707.1	n.276+6072C>T		intron_variant, non_coding_transcript_variant		3
TSHZ3	ENST00000651361.1	n.63+49764C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.517

Alfa AF: 0.455 Hom.: 21680

Bravo AF: 0.535

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.066
DANN	Benign	0.65

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: rs11883254; hg19: chr19-31790322;