20-53316174-A-C

Variant names:

• chr20-53316174-A-C
• rs200654
• NM_173485.6:c.*8+59603A>C

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+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
• Publications: 0 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=-0.89).
• 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 rank	MANE	Protein	UniProt
TSHZ2	NM_173485.6	c.*8+59603A>C		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+59603A>C		intron_variant	Intron 2 of 2	1	NM_173485.6	ENSP00000360552.3
TSHZ2	ENST00000603338.2	c.*8+59603A>C		intron_variant	Intron 2 of 2	2		ENSP00000475114.1
TSHZ2	ENST00000605656.2	n.*8+59603A>C		intron_variant	Intron 1 of 2	4		ENSP00000474159.2
ENSG00000271774	ENST00000606932.1	n.134-42793T>G		intron_variant	Intron 1 of 2	5

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

African (AFR) AF: 0.187 AC: 7772 AN: 41510

American (AMR) AF: 0.327 AC: 5001 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1741 AN: 5174

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4814

European-Finnish (FIN) AF: 0.508 AC: 5351 AN: 10536

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30300 AN: 67962

Other (OTH) AF: 0.327 AC: 691 AN: 2110

Alfa AF: 0.401 Hom.: 21592

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
PhyloP100		0.077
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: rs200654; hg19: chr20-51932713;