chr10-122849268-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152644.3(FAM24B):ā€‹c.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

Scores

5
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
Variant links:
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]

Genome browser will be placed here

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
FAM24BNM_152644.3 linkuse as main transcriptc.264C>G p.Cys88Trp missense_variant 4/4 ENST00000368898.8
FAM24B-CUZD1NR_037915.1 linkuse as main transcriptn.300-3048C>G intron_variant, non_coding_transcript_variant
FAM24BNM_001204364.1 linkuse as main transcriptc.264C>G p.Cys88Trp missense_variant 4/4
FAM24BNR_037911.1 linkuse as main transcriptn.471C>G non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAM24BENST00000368898.8 linkuse as main transcriptc.264C>G p.Cys88Trp missense_variant 4/41 NM_152644.3 P1
FAM24BENST00000368896.1 linkuse as main transcriptc.264C>G p.Cys88Trp missense_variant 4/42 P1
FAM24BENST00000462859.5 linkuse as main transcriptn.471C>G non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000423
AC:
6
AN:
1417774
Hom.:
0
Cov.:
30
AF XY:
0.00000428
AC XY:
3
AN XY:
700198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000553
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsSep 26, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.26
T;T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.65
.;T
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Benign
-0.53
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-9.6
D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0090
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.90
MutPred
0.51
Gain of solvent accessibility (P = 0.0133);Gain of solvent accessibility (P = 0.0133);
MVP
0.45
MPC
1.1
ClinPred
0.99
D
GERP RS
2.0
Varity_R
0.34
gMVP
0.063

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758502475; hg19: chr10-124608784; API