rs1353540

Variant names:

• chr19-31207281-C-A
• rs1353540
• ENST00000589511.2:n.517-218C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-31207281-C-A
• chr19-31207281-C-G
• chr19-31207281-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_138035.2(TSHZ3):​n.393+20724G>T variant causes a intron change. The variant allele was found at a frequency of 0.718 in 152,128 control chromosomes in the GnomAD database, including 39,804 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 0.72 (39804 hom., cov: 33)
• Consequence: TSHZ3 NR_138035.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• Publications: 2 publications found

Genes affected

LINC01791 (HGNC:52581): (long intergenic non-protein coding RNA 1791)

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_138035.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ3	NR_138035.2		n.393+20724G>T		intron	N/A
	TSHZ3	NR_138036.2		n.394-2203G>T		intron	N/A
	LINC01791	NR_147209.1		n.519-218C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC01791	ENST00000589511.2	TSL:5	n.517-218C>A		intron	N/A
	TSHZ3	ENST00000651361.1		n.687-2203G>T		intron	N/A
	LINC01791	ENST00000654096.1		n.197-3876C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109190 AN: 152010 Hom.: 39746 Cov.: 33

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.718 AC: 109303 AN: 152128 Hom.: 39804 Cov.: 33 AF XY: 0.717 AC XY: 53313 AN XY: 74366

African (AFR) AF: 0.847 AC: 35174 AN: 41510

American (AMR) AF: 0.726 AC: 11094 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2576 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3052 AN: 5180

South Asian (SAS) AF: 0.688 AC: 3317 AN: 4818

European-Finnish (FIN) AF: 0.629 AC: 6654 AN: 10572

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45241 AN: 67986

Other (OTH) AF: 0.686 AC: 1447 AN: 2110

Alfa AF: 0.711 Hom.: 6784

Bravo AF: 0.732

Asia WGS AF: 0.643 AC: 2232 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.62
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1353540; hg19: chr19-31698187;