14-51689882-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001267046.2(FRMD6):c.46C>T(p.Arg16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,560 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: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
FRMD6
NM_001267046.2 missense
NM_001267046.2 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 3.07
Genes affected
FRMD6 (HGNC:19839): (FERM domain containing 6) Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within apical constriction; cellular protein localization; and regulation of actin filament-based process. Predicted to be located in apical junction complex. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]
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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, 0.846
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD6 | NM_001267046.2 | c.46C>T | p.Arg16Cys | missense_variant | 2/14 | ENST00000344768.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD6 | ENST00000344768.10 | c.46C>T | p.Arg16Cys | missense_variant | 2/14 | 2 | NM_001267046.2 | ||
FRMD6 | ENST00000356218.8 | c.46C>T | p.Arg16Cys | missense_variant | 3/15 | 1 | P1 | ||
FRMD6 | ENST00000395718.6 | c.46C>T | p.Arg16Cys | missense_variant | 2/14 | 1 | P1 | ||
FRMD6 | ENST00000554778.1 | c.46C>T | p.Arg16Cys | missense_variant | 2/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152148Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251206Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135756
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GnomAD4 exome AF: 0.000152 AC: 222AN: 1461294Hom.: 0 Cov.: 29 AF XY: 0.000162 AC XY: 118AN XY: 727000
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN 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 | Jan 17, 2023 | The c.46C>T (p.R16C) alteration is located in exon 3 (coding exon 1) of the FRMD6 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the arginine (R) at amino acid position 16 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;D;.
Vest4
MVP
MPC
0.64
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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