NM_001018071.4:c.3910C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001018071.4(FRMPD2):c.3910C>T(p.Leu1304Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000028 ( 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: 1.31

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12156606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 link	c.3910C>T	p.Leu1304Phe	missense_variant	Exon 29 of 29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 link	c.3835C>T	p.Leu1279Phe	missense_variant	Exon 27 of 27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 link	c.943C>T	p.Leu315Phe	missense_variant	Exon 6 of 6		NP_001035977.3	Q68DX3-4
FRMPD2	XM_017015744.2 link	c.766C>T	p.Leu256Phe	missense_variant	Exon 6 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.3910C>T	p.Leu1304Phe	missense_variant	Exon 29 of 29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

144638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000457

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000283

AC:

AN:

670538

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

362362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17948

American (AMR)

AF:

0.00

AC:

AN:

43418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20782

East Asian (EAS)

AF:

0.00

AC:

AN:

35864

South Asian (SAS)

AF:

0.00

AC:

AN:

69814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52574

Middle Eastern (MID)

AF:

0.000396

AC:

AN:

2528

European-Non Finnish (NFE)

AF:

0.0000457

AC:

AN:

393690

Other (OTH)

AF:

0.00

AC:

AN:

33920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000207

AC:

AN:

144638

Hom.:

Cov.:

AF XY:

0.0000285

AC XY:

AN XY:

70182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38878

American (AMR)

AF:

0.00

AC:

AN:

14520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.00

AC:

AN:

4712

South Asian (SAS)

AF:

0.00

AC:

AN:

4526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000457

AC:

AN:

65690

Other (OTH)

AF:

0.00

AC:

AN:

1942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 05, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3910C>T (p.L1304F) alteration is located in exon 29 (coding exon 29) of the FRMPD2 gene. This alteration results from a C to T substitution at nucleotide position 3910, causing the leucine (L) at amino acid position 1304 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

0.088

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.086

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.97

L;.

PhyloP100

1.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.034

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.079

T;T

Polyphen

0.42

B;P

Vest4

0.13

MutPred

0.22

Loss of stability (P = 0.0582);.;

MVP

0.58

MPC

2.8

ClinPred

0.62

GERP RS

2.4

Varity_R

0.076

gMVP

0.087

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001018071.4:c.3910C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over