10-48172969-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001018071.4(FRMPD2):c.3200C>T(p.Ser1067Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000078 ( 0 hom., cov: 19)
Exomes 𝑓: 0.000039 ( 13 hom. )
Failed GnomAD Quality Control
Consequence
FRMPD2
NM_001018071.4 missense
NM_001018071.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.0160
Genes affected
FRMPD2 (HGNC:28572): (FERM and PDZ domain containing 2) This gene encodes a peripheral membrane protein and is located in a region of chromosome 10q that contains a segmental duplication. This copy of the gene is full-length and is in the telomeric duplicated region. Two other more centromerically proximal copies of the gene are partial and may represent pseudogenes. This full-length gene appears to function in the establishment and maintenance of cell polarization. The protein is recruited to cell-cell junctions in an E-cadherin-dependent manner, and is selectively localized at the basolateral membrane in polarized epithelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMPD2 | NM_001018071.4 | c.3200C>T | p.Ser1067Leu | missense_variant | 25/29 | ENST00000374201.8 | |
FRMPD2 | NM_001318191.1 | c.3125C>T | p.Ser1042Leu | missense_variant | 23/27 | ||
FRMPD2 | NM_001042512.3 | c.233C>T | p.Ser78Leu | missense_variant | 2/6 | ||
FRMPD2 | XM_017015744.2 | c.56C>T | p.Ser19Leu | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMPD2 | ENST00000374201.8 | c.3200C>T | p.Ser1067Leu | missense_variant | 25/29 | 1 | NM_001018071.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000785 AC: 1AN: 127414Hom.: 0 Cov.: 19
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GnomAD3 exomes AF: 0.0000682 AC: 15AN: 219952Hom.: 5 AF XY: 0.0000673 AC XY: 8AN XY: 118788
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000395 AC: 43AN: 1089760Hom.: 13 Cov.: 23 AF XY: 0.0000401 AC XY: 22AN XY: 549232
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GnomAD4 genome AF: 0.00000785 AC: 1AN: 127414Hom.: 0 Cov.: 19 AF XY: 0.0000163 AC XY: 1AN XY: 61312
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2022 | The c.3200C>T (p.S1067L) alteration is located in exon 25 (coding exon 25) of the FRMPD2 gene. This alteration results from a C to T substitution at nucleotide position 3200, causing the serine (S) at amino acid position 1067 to be replaced by a leucine (L). 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
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Benign
.;T;T
Sift4G
Benign
.;T;T
Polyphen
0.045, 0.024
.;B;B
Vest4
0.056, 0.042
MVP
0.12
MPC
1.5
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 26
Find out detailed SpliceAI scores and Pangolin per-transcript scores at