chr20-53016962-A-G

Variant names:

• chr20-53016962-A-G
• rs2256551
• NM_173485.6:c.40+43629A>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.40+43629A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,944 control chromosomes in the GnomAD database, including 22,797 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 0.54 (22797 hom., cov: 32)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 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.40+43629A>G		intron	N/A	NP_775756.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ2	ENST00000371497.10	TSL:1 MANE Select	c.40+43629A>G		intron	N/A	ENSP00000360552.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81561 AN: 151826 Hom.: 22767 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.537 AC: 81642 AN: 151944 Hom.: 22797 Cov.: 32 AF XY: 0.538 AC XY: 39938 AN XY: 74260

African (AFR) AF: 0.662 AC: 27427 AN: 41436

American (AMR) AF: 0.568 AC: 8665 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3468

East Asian (EAS) AF: 0.754 AC: 3887 AN: 5158

South Asian (SAS) AF: 0.668 AC: 3207 AN: 4802

European-Finnish (FIN) AF: 0.397 AC: 4198 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31410 AN: 67938

Other (OTH) AF: 0.493 AC: 1041 AN: 2110

Alfa AF: 0.507 Hom.: 4685

Bravo AF: 0.555

Asia WGS AF: 0.686 AC: 2382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.56
PhyloP100		-1.2
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: rs2256551; hg19: chr20-51633501;