9-37724246-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014907.3(FRMPD1):​c.538C>T​(p.Pro180Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FRMPD1
NM_014907.3 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39
Variant links:
Genes affected
FRMPD1 (HGNC:29159): (FERM and PDZ domain containing 1) Involved in establishment of protein localization to membrane and regulation of G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of protein-containing complex. Colocalizes with cell cortex. [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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRMPD1NM_014907.3 linkc.538C>T p.Pro180Ser missense_variant Exon 7 of 16 ENST00000377765.8 NP_055722.2 Q5SYB0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRMPD1ENST00000377765.8 linkc.538C>T p.Pro180Ser missense_variant Exon 7 of 16 1 NM_014907.3 ENSP00000366995.3 Q5SYB0-1
FRMPD1ENST00000539465.5 linkc.538C>T p.Pro180Ser missense_variant Exon 7 of 16 1 ENSP00000444411.1 Q5SYB0-1
ENSG00000255872ENST00000540557.1 linkn.*1011+3682G>A intron_variant Intron 10 of 11 5 ENSP00000457548.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1442080
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
718516
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.538C>T (p.P180S) alteration is located in exon 7 (coding exon 6) of the FRMPD1 gene. This alteration results from a C to T substitution at nucleotide position 538, causing the proline (P) at amino acid position 180 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.070
T;T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Uncertain
0.089
D
MetaRNN
Pathogenic
0.78
D;D
MetaSVM
Uncertain
0.10
D
MutationAssessor
Benign
1.9
L;L
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-7.6
D;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0020
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.83
MutPred
0.44
Gain of catalytic residue at P180 (P = 0.0021);Gain of catalytic residue at P180 (P = 0.0021);
MVP
0.92
MPC
0.64
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.73
gMVP
0.61

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

LitVar

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

Other links and lift over

dbSNP: rs865879056; hg19: chr9-37724243; API