Genetic Variant FRMPD2:p.Cys1164Phe (chr10-48168641-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001018071.4(FRMPD2):c.3491G>T(p.Cys1164Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 15)

Exomes 𝑓: 0.0000020 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

Publications

0 publications found

Variant links:

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]

FRMPD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 link	c.3491G>T	p.Cys1164Phe	missense_variant	Exon 27 of 29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 link	c.3416G>T	p.Cys1139Phe	missense_variant	Exon 25 of 27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 link	c.524G>T	p.Cys175Phe	missense_variant	Exon 4 of 6		NP_001035977.3	Q68DX3-4
FRMPD2	XM_017015744.2 link	c.347G>T	p.Cys116Phe	missense_variant	Exon 4 of 6		XP_016871233.1	Q68DX3-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8 link	c.3491G>T	p.Cys1164Phe	missense_variant	Exon 27 of 29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000108

AC:

AN:

184580

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000679

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000197

AC:

AN:

1016530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

508184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29452

American (AMR)

AF:

0.0000531

AC:

AN:

37692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16992

East Asian (EAS)

AF:

0.00

AC:

AN:

31128

South Asian (SAS)

AF:

0.00

AC:

AN:

72818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2906

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

748252

Other (OTH)

AF:

0.00

AC:

AN:

42610

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3491G>T (p.C1164F) alteration is located in exon 27 (coding exon 27) of the FRMPD2 gene. This alteration results from a G to T substitution at nucleotide position 3491, causing the cysteine (C) at amino acid position 1164 to be replaced by a phenylalanine (F). 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

Benign

0.29

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.86

D;T;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.8

.;M;.

PhyloP100

3.1

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-9.0

.;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0040

.;D;D

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

0.99, 0.92

.;D;P

Vest4

0.68, 0.69

MutPred

0.39

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;

MVP

0.45

MPC

3.4

ClinPred

0.99

GERP RS

1.3

Varity_R

0.55

gMVP

0.45

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over