rs200654

chr20-53316174-A-Cchr20-53316174-A-T

Variant summary

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

The NM_173485.6(TSHZ2):c.*8+59603A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,058 control chromosomes in the GnomAD database, including 10,726 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 0.36 (10726 hom., cov: 32)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ2	NM_173485.6	c.*8+59603A>C		intron_variant		ENST00000371497.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ2	ENST00000371497.10	c.*8+59603A>C		intron_variant		1	NM_173485.6	P1
	ENST00000606932.1	n.134-42793T>G		intron_variant, non_coding_transcript_variant		5
TSHZ2	ENST00000603338.2	c.*8+59603A>C		intron_variant		2
TSHZ2	ENST00000605656.2	c.*8+59603A>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54218 AN: 151940 Hom.: 10729 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.357 AC: 54220 AN: 152058 Hom.: 10726 Cov.: 32 AF XY: 0.354 AC XY: 26295 AN XY: 74306

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.327

Alfa AF: 0.408 Hom.: 17517

Bravo AF: 0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.76

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: rs200654; hg19: chr20-51932713;