18-75211879-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001308210.2(TSHZ1):c.3G>A(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TSHZ1
NM_001308210.2 start_lost
NM_001308210.2 start_lost
Scores
1
4
5
Clinical Significance
Conservation
PhyloP100: 5.24
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSHZ1 | NM_001308210.2 | c.3G>A | p.Met1? | start_lost | 1/2 | ENST00000580243.3 | |
TSHZ1 | NM_005786.6 | c.-96+636G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSHZ1 | ENST00000580243.3 | c.3G>A | p.Met1? | start_lost | 1/2 | 2 | NM_001308210.2 | P1 | |
TSHZ1 | ENST00000322038.5 | c.-96+636G>A | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1040860Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 491016
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1040860
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
491016
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Aural atresia, congenital Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 13, 2019 | The TSHZ1 c.3G>A p.(Met1?) variant alters the initiator methionine amino acid and the resultant protein is described as p.Met1? to denote that whether the loss of the methionine at codon 1 prevents all protein translation or causes abnormal protein formation from an alternate methionine is unknown. To our knowledge, this variant has not been reported in the peer-reviewed literature. The highest frequency of this allele in the Genome Aggregation Database is 0.00027 in the Admixed American population (version 2.1.1). Based on the limited evidence, the TSHZ1 c.3G>A p.(Met1?) variant is classified as a variant of uncertain significance for congenital aural atresia. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MutationTaster
Benign
D;D
Sift4G
Benign
T
Vest4
MVP
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.