NM_001388459.1:c.290C>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001388459.1(FRMPD3):​c.290C>A​(p.Thr97Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000366 in 1,092,494 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts 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. T97S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Consequence

FRMPD3
NM_001388459.1 missense

Scores

4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59
Variant links:
Genes affected
FRMPD3 (HGNC:29382): (FERM and PDZ domain containing 3) This gene encodes a protein that contains a PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain at the N-terminus followed by a FERM domain. The encoded protein is involved in signal transduction. The PDZ domain is thought to function in protein-protein interactions, mainly by binding to specific C-terminal peptides of other proteins. The FERM domain is found in proteins that are localized to the plasma membrane and are associated with the cytoskeleton. [provided by RefSeq, May 2017]
FRMPD3-AS1 (HGNC:41239): (FRMPD3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.25659898).
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRMPD3NM_001388459.1 linkc.290C>A p.Thr97Asn missense_variant Exon 4 of 15 ENST00000683843.1 NP_001375388.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRMPD3ENST00000683843.1 linkc.290C>A p.Thr97Asn missense_variant Exon 4 of 15 NM_001388459.1 ENSP00000507942.1 A0A804HKI5

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000366
AC:
4
AN:
1092494
Hom.:
0
Cov.:
28
AF XY:
0.00000836
AC XY:
3
AN XY:
358716
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:
0.00
Gnomad4 NFE exome
AF:
0.00000477
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.014
T;T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.78
T;T
M_CAP
Uncertain
0.28
D
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.1
L;.
PROVEAN
Uncertain
-2.5
N;N
REVEL
Benign
0.048
Sift
Benign
0.23
T;T
Sift4G
Benign
0.090
T;T
Vest4
0.73
MutPred
0.41
Gain of relative solvent accessibility (P = 0.0479);.;
MVP
0.51
MPC
0.16
ClinPred
0.67
D
GERP RS
4.6
Varity_R
0.42
gMVP
0.34

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: chrX-106776773; API