16-1827617-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_031208.4(FAHD1):c.379C>T(p.Pro127Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000299 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 0 hom. )
Consequence
FAHD1
NM_031208.4 missense
NM_031208.4 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.956
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAHD1 | NM_031208.4 | c.379C>T | p.Pro127Ser | missense_variant | 1/1 | ENST00000427358.5 | NP_112485.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FAHD1 | ENST00000427358.5 | c.379C>T | p.Pro127Ser | missense_variant | 1/1 | NM_031208.4 | ENSP00000398053 | P1 | ||
FAHD1 | ENST00000382668.8 | c.379C>T | p.Pro127Ser | missense_variant | 1/2 | 1 | ENSP00000372114 | |||
FAHD1 | ENST00000382666.6 | c.379C>T | p.Pro127Ser | missense_variant | 1/3 | 2 | ENSP00000372112 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 250828Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135710
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GnomAD4 exome AF: 0.000309 AC: 451AN: 1461570Hom.: 0 Cov.: 32 AF XY: 0.000315 AC XY: 229AN XY: 727090
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GnomAD4 genome AF: 0.000210 AC: 32AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74364
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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 | Jun 03, 2022 | The c.388C>T (p.P130S) alteration is located in exon 1 (coding exon 1) of the FAHD1 gene. This alteration results from a C to T substitution at nucleotide position 388, causing the proline (P) at amino acid position 130 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;D;.
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;.
Vest4
MVP
MPC
0.65
ClinPred
D
GERP RS
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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