chr20-53306099-T-C

Position:

• chr20-53306099-T-C

Variant summary

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

The NM_173485.6(TSHZ2):​c.*8+49528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,000 control chromosomes in the GnomAD database, including 35,183 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 0.67 (35183 hom., cov: 31)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHZ2	NM_173485.6	c.*8+49528T>C		intron_variant		ENST00000371497.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHZ2	ENST00000371497.10	c.*8+49528T>C		intron_variant		1	NM_173485.6	P1
	ENST00000606932.1	n.134-32718A>G		intron_variant, non_coding_transcript_variant		5
TSHZ2	ENST00000603338.2	c.*8+49528T>C		intron_variant		2
TSHZ2	ENST00000605656.2	c.*8+49528T>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102072 AN: 151882 Hom.: 35148 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.672 AC: 102157 AN: 152000 Hom.: 35183 Cov.: 31 AF XY: 0.670 AC XY: 49741 AN XY: 74284

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.663

Alfa AF: 0.642 Hom.: 17360

Bravo AF: 0.675

Asia WGS AF: 0.531 AC: 1845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.1
DANN	Benign	0.52

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: rs1996017; hg19: chr20-51922638;