3-69182640-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015123.3(FRMD4B):c.1997C>T(p.Thr666Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
FRMD4B
NM_015123.3 missense
NM_015123.3 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 9.36
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.79
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD4B | NM_015123.3 | c.1997C>T | p.Thr666Met | missense_variant | 20/23 | ENST00000398540.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD4B | ENST00000398540.8 | c.1997C>T | p.Thr666Met | missense_variant | 20/23 | 1 | NM_015123.3 | P1 | |
FRMD4B | ENST00000478263.5 | c.953C>T | p.Thr318Met | missense_variant | 10/13 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249152Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135166
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461524Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 727070
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152296Hom.: 1 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74456
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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 | Jul 09, 2021 | The c.1997C>T (p.T666M) alteration is located in exon 20 (coding exon 20) of the FRMD4B gene. This alteration results from a C to T substitution at nucleotide position 1997, causing the threonine (T) at amino acid position 666 to be replaced by a methionine (M). 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
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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