rs201812

Variant names:

• chr20-53389444-A-C
• rs201812
• NM_173485.6:c.*9-97700A>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.*9-97700A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,144 control chromosomes in the GnomAD database, including 22,839 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 0.51 (22839 hom., cov: 33)
• Consequence: TSHZ2 NM_173485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHZ2	NM_173485.6	c.*9-97700A>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.*9-97700A>C		intron_variant	Intron 2 of 2	1	NM_173485.6	ENSP00000360552.3
TSHZ2	ENST00000603338.2	c.*9-97700A>C		intron_variant	Intron 2 of 2	2		ENSP00000475114.1
TSHZ2	ENST00000605656.2	n.*9-97700A>C		intron_variant	Intron 1 of 2	4		ENSP00000474159.2
ENSG00000271774	ENST00000606932.1	n.133+97698T>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77635 AN: 152026 Hom.: 22845 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.510 AC: 77605 AN: 152144 Hom.: 22839 Cov.: 33 AF XY: 0.502 AC XY: 37314 AN XY: 74386

African (AFR) AF: 0.233 AC: 9656 AN: 41500

American (AMR) AF: 0.502 AC: 7668 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1977 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1236 AN: 5176

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4822

European-Finnish (FIN) AF: 0.644 AC: 6805 AN: 10570

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46039 AN: 68006

Other (OTH) AF: 0.517 AC: 1090 AN: 2108

Alfa AF: 0.541 Hom.: 4457

Bravo AF: 0.486

Asia WGS AF: 0.322 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.81
PhyloP100		0.45
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: rs201812; hg19: chr20-52005983;