3-69181454-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015123.3(FRMD4B):c.2296T>A(p.Ser766Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000088 in 1,613,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000092 ( 0 hom. )
Consequence
FRMD4B
NM_015123.3 missense
NM_015123.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 5.22
Genes affected
FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20128188).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD4B | NM_015123.3 | c.2296T>A | p.Ser766Thr | missense_variant | 21/23 | ENST00000398540.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD4B | ENST00000398540.8 | c.2296T>A | p.Ser766Thr | missense_variant | 21/23 | 1 | NM_015123.3 | P1 | |
FRMD4B | ENST00000478263.5 | c.1252T>A | p.Ser418Thr | missense_variant | 11/13 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000528 AC: 8AN: 151460Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249264Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135224
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GnomAD4 exome AF: 0.0000917 AC: 134AN: 1461676Hom.: 0 Cov.: 37 AF XY: 0.0000963 AC XY: 70AN XY: 727116
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GnomAD4 genome ? AF: 0.0000528 AC: 8AN: 151460Hom.: 0 Cov.: 31 AF XY: 0.0000676 AC XY: 5AN XY: 73940
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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 06, 2023 | The c.2296T>A (p.S766T) alteration is located in exon 21 (coding exon 21) of the FRMD4B gene. This alteration results from a T to A substitution at nucleotide position 2296, causing the serine (S) at amino acid position 766 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Loss of helix (P = 0.0626);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at