18-75221232-A-G

Position:

• chr18-75221232-A-G

Variant summary

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

The NM_001308210.2(TSHZ1):​c.40+9316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,166 control chromosomes in the GnomAD database, including 13,261 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 0.40 (13261 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TSHZ1 NM_001308210.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

Genes affected

TSHZ1 (HGNC:10669): (teashirt zinc finger homeobox 1) This gene encodes a colon cancer antigen that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type zinc-finger protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene may be associated with congenital aural atresia syndrome. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHZ1	NM_001308210.2	c.40+9316A>G		intron_variant		ENST00000580243.3	NP_001295139.1
TSHZ1	NM_005786.6	c.-96+9989A>G		intron_variant			NP_005777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHZ1	ENST00000580243.3	c.40+9316A>G		intron_variant		2	NM_001308210.2	ENSP00000464391.1
TSHZ1	ENST00000322038.5	c.-96+9989A>G		intron_variant		1		ENSP00000323584.5
TSHZ1	ENST00000560918.2	c.-96+78A>G		intron_variant		4		ENSP00000453834.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 61013 AN: 152044 Hom.: 13227 Cov.: 33

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.402 AC: 61106 AN: 152166 Hom.: 13261 Cov.: 33 AF XY: 0.403 AC XY: 29999 AN XY: 74392

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.370

Alfa AF: 0.333 Hom.: 17911

Bravo AF: 0.410

Asia WGS AF: 0.414 AC: 1436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.51

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: rs1866732; hg19: chr18-72933187;