chr15-43883748-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_032892.5(FRMD5):c.1090G>A(p.Val364Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,728 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
FRMD5
NM_032892.5 missense
NM_032892.5 missense
Scores
5
10
Clinical Significance
Conservation
PhyloP100: 5.52
Genes affected
FRMD5 (HGNC:28214): (FERM domain containing 5) Enables integrin binding activity and protein kinase binding activity. Involved in negative regulation of cell motility; positive regulation of cell adhesion; and regulation of cell migration. Located in adherens junction. [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 0 ACMG points.
PM1
?
In a region_of_interest Disordered (size 23) in uniprot entity FRMD5_HUMAN there are 12 pathogenic changes around while only 0 benign (100%) in NM_032892.5
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19100559).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD5 | NM_032892.5 | c.1090G>A | p.Val364Ile | missense_variant | 13/14 | ENST00000417257.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD5 | ENST00000417257.6 | c.1090G>A | p.Val364Ile | missense_variant | 13/14 | 1 | NM_032892.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152200
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250694Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135438
GnomAD3 exomes
AF:
AC:
4
AN:
250694
Hom.:
AF XY:
AC XY:
1
AN XY:
135438
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461528Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 727064
GnomAD4 exome
AF:
AC:
30
AN:
1461528
Hom.:
Cov.:
30
AF XY:
AC XY:
10
AN XY:
727064
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
GnomAD4 genome
?
AF:
AC:
4
AN:
152200
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74340
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.1090G>A (p.V364I) alteration is located in exon 13 (coding exon 13) of the FRMD5 gene. This alteration results from a G to A substitution at nucleotide position 1090, causing the valine (V) at amino acid position 364 to be replaced by an isoleucine (I). 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
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.23, 0.033
.;B;B;.;.
Vest4
MVP
MPC
0.73
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at