rs16997525

Variant names:

• chr20-53103883-T-C
• rs16997525
• NM_173485.6:c.40+130550T>C

Variant summary

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

The NM_173485.6(TSHZ2):​c.40+130550T>C variant causes a intron change. The variant allele was found at a frequency of 0.195 in 152,184 control chromosomes in the GnomAD database, including 3,620 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 0.20 (3620 hom., cov: 32)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ2	NM_173485.6	c.40+130550T>C		intron_variant	Intron 1 of 2	ENST00000371497.10	NP_775756.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ2	ENST00000371497.10	c.40+130550T>C		intron_variant	Intron 1 of 2	1	NM_173485.6	ENSP00000360552.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29647 AN: 152066 Hom.: 3611 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.195 AC: 29686 AN: 152184 Hom.: 3620 Cov.: 32 AF XY: 0.193 AC XY: 14383 AN XY: 74426

African (AFR) AF: 0.357 AC: 14791 AN: 41488

American (AMR) AF: 0.125 AC: 1909 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3470

East Asian (EAS) AF: 0.121 AC: 625 AN: 5180

South Asian (SAS) AF: 0.128 AC: 615 AN: 4822

European-Finnish (FIN) AF: 0.151 AC: 1600 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9325 AN: 68012

Other (OTH) AF: 0.166 AC: 348 AN: 2102

Alfa AF: 0.150 Hom.: 3164

Bravo AF: 0.201

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		4.7
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: rs16997525; hg19: chr20-51720422;