rs1293381

Positions:

• chr20-53192360-A-G

Variant summary

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

The NM_173485.6(TSHZ2):​c.41-61139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,574 control chromosomes in the GnomAD database, including 10,367 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 0.37 (10367 hom., cov: 30)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

Genes affected

TSHZ2 (HGNC:13010): (teashirt zinc finger homeobox 2) This gene is a member of the teashirt C2H2-type zinc-finger protein family of transcription factors. This gene encodes a protein with five C2H2-type zinc fingers, a homeobox DNA-binding domain and a coiled-coil domain. This nuclear protein is predicted to act as a transcriptional repressor. This gene is thought to play a role in the development and progression of breast and other types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ2	NM_173485.6	c.41-61139A>G		intron_variant		ENST00000371497.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ2	ENST00000371497.10	c.41-61139A>G		intron_variant		1	NM_173485.6	P1
TSHZ2	ENST00000603338.2	c.31+6684A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55336 AN: 151466 Hom.: 10350 Cov.: 30

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.365 AC: 55393 AN: 151574 Hom.: 10367 Cov.: 30 AF XY: 0.371 AC XY: 27442 AN XY: 74038

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.334

Alfa AF: 0.368 Hom.: 14157

Bravo AF: 0.358

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.60

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: rs1293381; hg19: chr20-51808899;