3-69180910-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015123.3(FRMD4B):​c.2840C>G​(p.Ser947Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,603,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.00047 ( 0 hom., cov: 31)
Exomes š‘“: 0.000050 ( 0 hom. )

Consequence

FRMD4B
NM_015123.3 missense

Scores

3
12
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60
Variant links:
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]

Genome browser will be placed here

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=0.2965697).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRMD4BNM_015123.3 linkc.2840C>G p.Ser947Trp missense_variant Exon 21 of 23 ENST00000398540.8 NP_055938.2 Q9Y2L6-1B3KNA2Q6PEW6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRMD4BENST00000398540.8 linkc.2840C>G p.Ser947Trp missense_variant Exon 21 of 23 1 NM_015123.3 ENSP00000381549.3 Q9Y2L6-1
FRMD4BENST00000478263.5 linkc.1796C>G p.Ser599Trp missense_variant Exon 11 of 13 1 ENSP00000418682.1 E9PGA7

Frequencies

GnomAD3 genomes
AF:
0.000467
AC:
71
AN:
152050
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000126
AC:
31
AN:
245344
Hom.:
0
AF XY:
0.000113
AC XY:
15
AN XY:
133070
show subpopulations
Gnomad AFR exome
AF:
0.00200
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000503
AC:
73
AN:
1451006
Hom.:
0
Cov.:
32
AF XY:
0.0000430
AC XY:
31
AN XY:
720548
show subpopulations
Gnomad4 AFR exome
AF:
0.00201
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000100
GnomAD4 genome
AF:
0.000467
AC:
71
AN:
152168
Hom.:
0
Cov.:
31
AF XY:
0.000565
AC XY:
42
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00169
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00000462
Hom.:
100217
ExAC
AF:
0.000166
AC:
20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.078
T;T
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Uncertain
0.66
D
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-2.4
N;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0080
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;.
Vest4
0.67
MVP
0.70
MPC
0.38
ClinPred
0.21
T
GERP RS
5.8
Varity_R
0.29
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9831516; hg19: chr3-69230061; API