chr20-53192360-A-G

Variant names:

• chr20-53192360-A-G
• rs1293381
• NM_173485.6:c.41-61139A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173485.6. 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
	TSHZ2	NM_173485.6	MANE Select	c.41-61139A>G		intron	N/A	NP_775756.3
	TSHZ2	NM_001193421.2		c.31+6684A>G		intron	N/A	NP_001180350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ2	ENST00000371497.10	TSL:1 MANE Select	c.41-61139A>G		intron	N/A	ENSP00000360552.3
	TSHZ2	ENST00000603338.2	TSL:2	c.31+6684A>G		intron	N/A	ENSP00000475114.1

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

African (AFR) AF: 0.305 AC: 12625 AN: 41360

American (AMR) AF: 0.378 AC: 5761 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1300 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2685 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2335 AN: 4784

European-Finnish (FIN) AF: 0.428 AC: 4430 AN: 10350

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25191 AN: 67882

Other (OTH) AF: 0.334 AC: 704 AN: 2108

Alfa AF: 0.367 Hom.: 17704

Bravo AF: 0.358

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		0.26
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: rs1293381; hg19: chr20-51808899;