10-48163340-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001018071.4(FRMPD2):c.3869T>G(p.Met1290Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000671 in 149,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.217

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024691284).

BP6

Variant 10-48163340-A-C is Benign according to our data. Variant chr10-48163340-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3097010.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FRMPD2	NM_001018071.4 linkuse as main transcript	c.3869T>G	p.Met1290Arg	missense_variant	28/29	ENST00000374201.8
FRMPD2	NM_001318191.1 linkuse as main transcript	c.3794T>G	p.Met1265Arg	missense_variant	26/27
FRMPD2	NM_001042512.3 linkuse as main transcript	c.902T>G	p.Met301Arg	missense_variant	5/6
FRMPD2	XM_017015744.2 linkuse as main transcript	c.725T>G	p.Met242Arg	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD2	ENST00000374201.8 linkuse as main transcript	c.3869T>G	p.Met1290Arg	missense_variant	28/29	1	NM_001018071.4	P2	Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

149054

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

245676

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000211

AC:

AN:

994172

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

514434

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:

0.0000305

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000671

AC:

AN:

149054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72678

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.031

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Benign

0.88

DEOGEN2

Benign

0.0035

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.35

T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.47

Polyphen

0.0

.;B;B

Vest4

0.23, 0.21

MutPred

0.43

Loss of stability (P = 0.0136);Loss of stability (P = 0.0136);.;

MVP

0.099

MPC

2.3

ClinPred

0.046

GERP RS

0.55

Varity_R

0.17

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over