8-134509731-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020863.4(ZFAT):c.3380C>T(p.Thr1127Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,608,072 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
ZFAT
NM_020863.4 missense
NM_020863.4 missense
Scores
6
10
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
ZFAT (HGNC:19899): (zinc finger and AT-hook domain containing) This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32545227).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFAT | NM_020863.4 | c.3380C>T | p.Thr1127Met | missense_variant | 15/16 | ENST00000377838.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFAT | ENST00000377838.8 | c.3380C>T | p.Thr1127Met | missense_variant | 15/16 | 1 | NM_020863.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151756Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00000822 AC: 2AN: 243392Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132356
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GnomAD4 exome AF: 0.0000117 AC: 17AN: 1456316Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 724716
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GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151756Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74092
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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 | Jan 23, 2023 | The c.3380C>T (p.T1127M) alteration is located in exon 15 (coding exon 15) of the ZFAT gene. This alteration results from a C to T substitution at nucleotide position 3380, causing the threonine (T) at amino acid position 1127 to be replaced by a methionine (M). 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
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;D;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.
Vest4
MutPred
0.36
.;.;Loss of helix (P = 0.0626);.;.;.;
MVP
MPC
0.75
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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