18-75221232-A-G

Variant names:

• chr18-75221232-A-G
• rs1866732
• NM_001308210.2:c.40+9316A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

TSHZ1 Gene-Disease associations (from GenCC):

• aural atresia, congenital

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308210.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	NM_001308210.2	MANE Select	c.40+9316A>G		intron	N/A	NP_001295139.1
	TSHZ1	NM_005786.6		c.-96+9989A>G		intron	N/A	NP_005777.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.40+9316A>G		intron	N/A	ENSP00000464391.1
	TSHZ1	ENST00000322038.5	TSL:1	c.-96+9989A>G		intron	N/A	ENSP00000323584.5
	TSHZ1	ENST00000560918.2	TSL:4	c.-96+78A>G		intron	N/A	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

African (AFR) AF: 0.575 AC: 23878 AN: 41512

American (AMR) AF: 0.361 AC: 5526 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 942 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2179 AN: 5180

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4824

European-Finnish (FIN) AF: 0.376 AC: 3973 AN: 10572

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22036 AN: 67998

Other (OTH) AF: 0.370 AC: 782 AN: 2116

Alfa AF: 0.346 Hom.: 40827

Bravo AF: 0.410

Asia WGS AF: 0.414 AC: 1436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-0.43
PromoterAI		-0.0087	Neutral
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: rs1866732; hg19: chr18-72933187;