20-53466315-G-T

Variant names:

• chr20-53466315-G-T
• rs6068555
• NM_173485.6:c.*9-20829G>T

Variant summary

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

The NM_173485.6(TSHZ2):​c.*9-20829G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,380 control chromosomes in the GnomAD database, including 25,516 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 0.57 (25516 hom., cov: 30)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 7 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]

ENSG00000259723 (HGNC:58099):

ENSG00000271774 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 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.*9-20829G>T		intron	N/A	NP_775756.3
	TSHZ2	NM_001193421.2		c.*9-20829G>T		intron	N/A	NP_001180350.1
	TSHZ2-AS1	NR_187666.1		n.211-4747C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ2	ENST00000371497.10	TSL:1 MANE Select	c.*9-20829G>T		intron	N/A	ENSP00000360552.3
	TSHZ2	ENST00000603338.2	TSL:2	c.*9-20829G>T		intron	N/A	ENSP00000475114.1
	ENSG00000259723	ENST00000558738.1	TSL:4	n.207-4747C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.574 AC: 86875 AN: 151268 Hom.: 25459 Cov.: 30

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.575 AC: 86991 AN: 151380 Hom.: 25516 Cov.: 30 AF XY: 0.582 AC XY: 43004 AN XY: 73908

African (AFR) AF: 0.690 AC: 28484 AN: 41256

American (AMR) AF: 0.587 AC: 8928 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1590 AN: 3454

East Asian (EAS) AF: 0.608 AC: 3134 AN: 5156

South Asian (SAS) AF: 0.634 AC: 3039 AN: 4792

European-Finnish (FIN) AF: 0.621 AC: 6431 AN: 10362

Middle Eastern (MID) AF: 0.572 AC: 166 AN: 290

European-Non Finnish (NFE) AF: 0.495 AC: 33574 AN: 67846

Other (OTH) AF: 0.561 AC: 1175 AN: 2096

Alfa AF: 0.507 Hom.: 48021

Bravo AF: 0.579

Asia WGS AF: 0.665 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.43
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: rs6068555; hg19: chr20-52082854;