rs376458726

Variant names:

• chr18-75210894-TGA-T
• rs376458726
• NM_001308210.2:c.-981_-980delAG

Your query was ambiguous. Multiple possible variants found:

• chr18-75210894-TGA-T
• chr18-75210894-TGA-TGAGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001308210.2(TSHZ1):​c.-981_-980delAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 88,446 control chromosomes in the GnomAD database, including 653 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (653 hom., cov: 14)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: TSHZ1 NM_001308210.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.00
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	NM_001308210.2	MANE Select	c.-981_-980delAG		5_prime_UTR	Exon 1 of 2	NP_001295139.1
	TSHZ1	NM_005786.6		c.-443_-442delAG		5_prime_UTR	Exon 1 of 2	NP_005777.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHZ1	ENST00000580243.3	TSL:2 MANE Select	c.-981_-980delAG		5_prime_UTR	Exon 1 of 2	ENSP00000464391.1
	TSHZ1	ENST00000322038.5	TSL:1	c.-443_-442delAG		5_prime_UTR	Exon 1 of 2	ENSP00000323584.5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 11437 AN: 88312 Hom.: 655 Cov.: 14

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00935

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.000766

Gnomad SAS AF: 0.0645

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0143 AC: 1 AN: 70 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0179 AC: 1 AN: 56

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.129 AC: 11438 AN: 88376 Hom.: 653 Cov.: 14 AF XY: 0.123 AC XY: 5278 AN XY: 42760

African (AFR) AF: 0.224 AC: 4753 AN: 21206

American (AMR) AF: 0.137 AC: 1296 AN: 9468

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 467 AN: 2696

East Asian (EAS) AF: 0.000769 AC: 2 AN: 2602

South Asian (SAS) AF: 0.0642 AC: 125 AN: 1946

European-Finnish (FIN) AF: 0.0179 AC: 103 AN: 5756

Middle Eastern (MID) AF: 0.313 AC: 60 AN: 192

European-Non Finnish (NFE) AF: 0.104 AC: 4422 AN: 42568

Other (OTH) AF: 0.157 AC: 204 AN: 1300

Alfa AF: 0.0708 Hom.: 36

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Aural atresia, congenital (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=300/0	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: rs376458726; hg19: chr18-72922849;