19-31277337-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_020856.4(TSHZ3):c.2456C>T(p.Ser819Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 0 hom. )
Consequence
TSHZ3
NM_020856.4 missense
NM_020856.4 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 9.55
Genes affected
TSHZ3 (HGNC:30700): (teashirt zinc finger homeobox 3) This gene encodes a zinc-finger transcription factor that regulates smooth muscle cell differentiation in the developing urinary tract. Consistent with this role, mice in which this gene has been inactivated exhibit abnormal gene expression in urinary tract smooth muscle cell precursors and kidney defects including hydronephrosis. The encoded transcription factor comprises a gene silencing complex that inhibits caspase expression. Reduced expression of this gene and consequent caspase upregulation may be correlated with progression of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1599288).
BS2
?
High AC in GnomAd at 44 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSHZ3 | NM_020856.4 | c.2456C>T | p.Ser819Leu | missense_variant | 2/2 | ENST00000240587.5 | |
TSHZ3 | XM_047439132.1 | c.2456C>T | p.Ser819Leu | missense_variant | 3/3 | ||
TSHZ3 | NR_138035.2 | n.258-49197C>T | intron_variant, non_coding_transcript_variant | ||||
TSHZ3 | NR_138036.2 | n.258-49197C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSHZ3 | ENST00000240587.5 | c.2456C>T | p.Ser819Leu | missense_variant | 2/2 | 1 | NM_020856.4 | P1 | |
TSHZ3 | ENST00000651361.1 | n.64-34462C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152262Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251338Hom.: 0 AF XY: 0.000272 AC XY: 37AN XY: 135828
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GnomAD4 exome AF: 0.000475 AC: 694AN: 1461552Hom.: 0 Cov.: 30 AF XY: 0.000472 AC XY: 343AN XY: 726996
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GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74390
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2022 | The c.2456C>T (p.S819L) alteration is located in exon 2 (coding exon 2) of the TSHZ3 gene. This alteration results from a C to T substitution at nucleotide position 2456, causing the serine (S) at amino acid position 819 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at