8-134478531-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_020863.4(ZFAT):c.3683T>C(p.Met1228Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00123 in 1,589,586 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1228L) has been classified as Uncertain significance.
Frequency
Consequence
NM_020863.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFAT | NM_020863.4 | c.3683T>C | p.Met1228Thr | missense_variant | 16/16 | ENST00000377838.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFAT | ENST00000377838.8 | c.3683T>C | p.Met1228Thr | missense_variant | 16/16 | 1 | NM_020863.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000802 AC: 122AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000590 AC: 123AN: 208596Hom.: 0 AF XY: 0.000577 AC XY: 65AN XY: 112734
GnomAD4 exome AF: 0.00128 AC: 1834AN: 1437316Hom.: 2 Cov.: 32 AF XY: 0.00123 AC XY: 879AN XY: 712548
GnomAD4 genome ? AF: 0.000801 AC: 122AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74476
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2023 | The c.3683T>C (p.M1228T) alteration is located in exon 16 (coding exon 16) of the ZFAT gene. This alteration results from a T to C substitution at nucleotide position 3683, causing the methionine (M) at amino acid position 1228 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at