chr20-53274851-G-A

Variant names:

• chr20-53274851-G-A
• rs6097326
• NM_173485.6:c.*8+18280G>A

Variant summary

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

The NM_173485.6(TSHZ2):​c.*8+18280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,926 control chromosomes in the GnomAD database, including 2,760 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 0.18 (2760 hom., cov: 32)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 3 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]

ENSG00000271774 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ2	NM_173485.6	c.*8+18280G>A		intron_variant	Intron 2 of 2	ENST00000371497.10	NP_775756.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHZ2	ENST00000371497.10	c.*8+18280G>A		intron_variant	Intron 2 of 2	1	NM_173485.6	ENSP00000360552.3
TSHZ2	ENST00000603338.2	c.*8+18280G>A		intron_variant	Intron 2 of 2	2		ENSP00000475114.1
TSHZ2	ENST00000605656.2	n.*8+18280G>A		intron_variant	Intron 1 of 2	4		ENSP00000474159.2
ENSG00000271774	ENST00000606932.1	n.134-1470C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27076 AN: 151808 Hom.: 2759 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.178 AC: 27097 AN: 151926 Hom.: 2760 Cov.: 32 AF XY: 0.180 AC XY: 13358 AN XY: 74238

African (AFR) AF: 0.279 AC: 11550 AN: 41420

American (AMR) AF: 0.165 AC: 2519 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3464

East Asian (EAS) AF: 0.104 AC: 536 AN: 5170

South Asian (SAS) AF: 0.228 AC: 1095 AN: 4808

European-Finnish (FIN) AF: 0.162 AC: 1699 AN: 10520

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8661 AN: 67954

Other (OTH) AF: 0.171 AC: 359 AN: 2102

Alfa AF: 0.145 Hom.: 3121

Bravo AF: 0.183

Asia WGS AF: 0.178 AC: 620 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	0.15
DANN	Benign	0.65
PhyloP100		-2.3
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: rs6097326; hg19: chr20-51891390;