10-14521258-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031453.4(FAM107B):​c.853G>A​(p.Glu285Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,838 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FAM107B
NM_031453.4 missense

Scores

13
4
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09
Variant links:
Genes affected
FAM107B (HGNC:23726): (family with sequence similarity 107 member B) Predicted to act upstream of or within sensory perception of sound. [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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM107BNM_031453.4 linkc.853G>A p.Glu285Lys missense_variant Exon 5 of 5 ENST00000181796.7 NP_113641.2 Q9H098-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM107BENST00000181796.7 linkc.853G>A p.Glu285Lys missense_variant Exon 5 of 5 2 NM_031453.4 ENSP00000181796.2 Q9H098-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461838
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727222
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.853G>A (p.E285K) alteration is located in exon 5 (coding exon 5) of the FAM107B gene. This alteration results from a G to A substitution at nucleotide position 853, causing the glutamic acid (E) at amino acid position 285 to be replaced by a lysine (K). 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
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.37
T;T;.;T;T;T;T;T;T;T;T;.;T;T;T
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
.;D;D;.;.;.;.;.;.;.;.;D;D;D;D
M_CAP
Uncertain
0.086
D
MetaRNN
Pathogenic
0.90
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.0099
T
MutationAssessor
Uncertain
2.8
M;M;.;M;M;M;M;M;M;M;M;.;.;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-3.5
D;.;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.71
Sift
Pathogenic
0.0
D;.;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;.;.;.;.
Polyphen
1.0
D;D;D;D;D;D;D;D;D;D;D;.;.;.;.
Vest4
0.90
MutPred
0.74
Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);.;Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);Gain of methylation at E110 (P = 0.0014);
MVP
0.82
MPC
0.64
ClinPred
1.0
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.83
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-14563257; COSMIC: COSV51680691; COSMIC: COSV51680691; API