chr5-141644382-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033449.3(FCHSD1):c.1699T>C(p.Phe567Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
FCHSD1
NM_033449.3 missense
NM_033449.3 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 8.91
Genes affected
FCHSD1 (HGNC:25463): (FCH and double SH3 domains 1) Predicted to enable lipid binding activity. Predicted to be involved in neuromuscular synaptic transmission and positive regulation of actin filament polymerization. Predicted to be located in cell projection and perikaryon. Predicted to be active in neuromuscular junction and recycling endosome. Predicted to colocalize with cuticular plate. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCHSD1 | NM_033449.3 | c.1699T>C | p.Phe567Leu | missense_variant | 17/20 | ENST00000435817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCHSD1 | ENST00000435817.7 | c.1699T>C | p.Phe567Leu | missense_variant | 17/20 | 1 | NM_033449.3 | P1 | |
FCHSD1 | ENST00000522783.5 | c.1477T>C | p.Phe493Leu | missense_variant | 16/20 | 5 | |||
FCHSD1 | ENST00000523856.5 | n.1368T>C | non_coding_transcript_exon_variant | 8/11 | 2 | ||||
FCHSD1 | ENST00000522126.5 | c.*237T>C | 3_prime_UTR_variant, NMD_transcript_variant | 16/19 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.000273 AC: 68AN: 249008Hom.: 0 AF XY: 0.000259 AC XY: 35AN XY: 135110
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GnomAD4 exome AF: 0.000133 AC: 194AN: 1461666Hom.: 0 Cov.: 33 AF XY: 0.000128 AC XY: 93AN XY: 727114
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74332
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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 | Dec 28, 2023 | The c.1699T>C (p.F567L) alteration is located in exon 17 (coding exon 17) of the FCHSD1 gene. This alteration results from a T to C substitution at nucleotide position 1699, causing the phenylalanine (F) at amino acid position 567 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
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;T
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of disorder (P = 0.0991);.;
MVP
MPC
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