14-51720124-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001267046.2(FRMD6):c.1094G>T(p.Arg365Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,613,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
FRMD6
NM_001267046.2 missense
NM_001267046.2 missense
Scores
1
7
8
Clinical Significance
Conservation
PhyloP100: 5.07
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36515644).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD6 | NM_001267046.2 | c.1094G>T | p.Arg365Leu | missense_variant | 11/14 | ENST00000344768.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD6 | ENST00000344768.10 | c.1094G>T | p.Arg365Leu | missense_variant | 11/14 | 2 | NM_001267046.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000324 AC: 8AN: 247062Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133932
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461518Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727020
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74312
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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 21, 2021 | The c.1070G>T (p.R357L) alteration is located in exon 12 (coding exon 10) of the FRMD6 gene. This alteration results from a G to T substitution at nucleotide position 1070, causing the arginine (R) at amino acid position 357 to be replaced by a leucine (L). 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
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;D;D
Sift4G
Benign
T;T;T;T;T;D;D
Polyphen
D;D;D;D;.;.;.
Vest4
MVP
MPC
0.22
ClinPred
T
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