rs372787732

Variant names:

• chr18-75210896-AGG-A
• rs372787732
• NM_001308210.2:c.-971_-970delGG

Your query was ambiguous. Multiple possible variants found:

• chr18-75210896-AGG-A
• chr18-75210896-AGG-AG
• chr18-75210896-AGG-AGGG
• chr18-75210896-AGG-AGGGG
• chr18-75210896-AGG-AGGGGG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001308210.2(TSHZ1):​c.-971_-970delGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000751 in 79,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., cov: 0)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: TSHZ1 NM_001308210.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• 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: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

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.-971_-970delGG		5_prime_UTR	Exon 1 of 2	NP_001295139.1	Q6ZSZ6-1
	TSHZ1	NM_005786.6		c.-433_-432delGG		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.-971_-970delGG		5_prime_UTR	Exon 1 of 2	ENSP00000464391.1	Q6ZSZ6-1
	TSHZ1	ENST00000322038.5	TSL:1	c.-433_-432delGG		5_prime_UTR	Exon 1 of 2	ENSP00000323584.5	Q6ZSZ6-2

Frequencies

GnomAD3 genomes AF: 0.0000626 AC: 5 AN: 79824 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000962

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000759

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0556 AC: 1 AN: 18 Hom.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 1 AN: 14

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000626 AC: 5 AN: 79824 Hom.: 0 Cov.: 0 AF XY: 0.0000264 AC XY: 1 AN XY: 37848

African (AFR) AF: 0.0000962 AC: 2 AN: 20782

American (AMR) AF: 0.00 AC: 0 AN: 7516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1768

East Asian (EAS) AF: 0.00 AC: 0 AN: 2602

South Asian (SAS) AF: 0.00 AC: 0 AN: 1964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 122

European-Non Finnish (NFE) AF: 0.0000759 AC: 3 AN: 39508

Other (OTH) AF: 0.00 AC: 0 AN: 1006

Alfa AF: 0.00 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16
Mutation Taster		=300/0	polymorphism

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: rs372787732; hg19: chr18-72922851;