rs10485815

Positions:

• chr20-53046949-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173485.6(TSHZ2):​c.40+73616C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,020 control chromosomes in the GnomAD database, including 7,747 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 0.24 (7747 hom., cov: 32)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ2	NM_173485.6	c.40+73616C>T		intron_variant		ENST00000371497.10	NP_775756.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ2	ENST00000371497.10	c.40+73616C>T		intron_variant		1	NM_173485.6	ENSP00000360552	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36553 AN: 151902 Hom.: 7727 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.241 AC: 36603 AN: 152020 Hom.: 7747 Cov.: 32 AF XY: 0.240 AC XY: 17824 AN XY: 74316

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0966

Gnomad4 OTH AF: 0.188

Alfa AF: 0.118 Hom.: 2979

Bravo AF: 0.256

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.066
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs10485815; hg19: chr20-51663488;