chr10-122849268-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_152644.3(FAM24B):āc.264C>Gā(p.Cys88Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,417,774 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000042 ( 0 hom. )
Consequence
FAM24B
NM_152644.3 missense
NM_152644.3 missense
Scores
5
5
8
Clinical Significance
Conservation
PhyloP100: 1.25
Genes affected
FAM24B (HGNC:23475): (family with sequence similarity 24 member B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.819
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAM24B | NM_152644.3 | c.264C>G | p.Cys88Trp | missense_variant | 4/4 | ENST00000368898.8 | |
FAM24B-CUZD1 | NR_037915.1 | n.300-3048C>G | intron_variant, non_coding_transcript_variant | ||||
FAM24B | NM_001204364.1 | c.264C>G | p.Cys88Trp | missense_variant | 4/4 | ||
FAM24B | NR_037911.1 | n.471C>G | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM24B | ENST00000368898.8 | c.264C>G | p.Cys88Trp | missense_variant | 4/4 | 1 | NM_152644.3 | P1 | |
FAM24B | ENST00000368896.1 | c.264C>G | p.Cys88Trp | missense_variant | 4/4 | 2 | P1 | ||
FAM24B | ENST00000462859.5 | n.471C>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000423 AC: 6AN: 1417774Hom.: 0 Cov.: 30 AF XY: 0.00000428 AC XY: 3AN XY: 700198
GnomAD4 exome
AF:
AC:
6
AN:
1417774
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Cov.:
30
AF XY:
AC XY:
3
AN XY:
700198
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | Sep 26, 2023 | The c.264C>G (p.C88W) alteration is located in exon 4 (coding exon 2) of the FAM24B gene. This alteration results from a C to G substitution at nucleotide position 264, causing the cysteine (C) at amino acid position 88 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0133);Gain of solvent accessibility (P = 0.0133);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at