rs145347617

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024919.6(FRMD1):​c.1399G>T​(p.Val467Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,423,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V467M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FRMD1
NM_024919.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.992
Variant links:
Genes affected
FRMD1 (HGNC:21240): (FERM domain containing 1) Predicted to be involved in positive regulation of hippo signaling. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasmic side of apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03423834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRMD1NM_024919.6 linkc.1399G>T p.Val467Leu missense_variant Exon 10 of 11 ENST00000283309.11 NP_079195.3 Q8N878-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRMD1ENST00000283309.11 linkc.1399G>T p.Val467Leu missense_variant Exon 10 of 11 1 NM_024919.6 ENSP00000283309.6 Q8N878-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.03e-7
AC:
1
AN:
1423002
Hom.:
0
Cov.:
35
AF XY:
0.00000142
AC XY:
1
AN XY:
705214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000236
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.0070
DANN
Benign
0.61
DEOGEN2
Benign
0.00093
.;.;T;.;.
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.41
T;T;T;T;T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.034
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;.;N;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.95
.;.;N;N;.
REVEL
Benign
0.020
Sift
Benign
1.0
.;.;T;T;.
Sift4G
Benign
1.0
.;.;T;T;.
Polyphen
0.0, 0.0010
.;.;B;B;.
Vest4
0.040, 0.033
MutPred
0.26
.;.;Gain of helix (P = 0.062);.;.;
MVP
0.12
MPC
0.098
ClinPred
0.086
T
GERP RS
-1.4
Varity_R
0.049
gMVP
0.072

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-168459812; API