chr10-48163430-C-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.3779G>A(p.Cys1260Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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=0.07063162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 link	c.3779G>A	p.Cys1260Tyr	missense_variant	Exon 28 of 29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 link	c.3704G>A	p.Cys1235Tyr	missense_variant	Exon 26 of 27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 link	c.812G>A	p.Cys271Tyr	missense_variant	Exon 5 of 6		NP_001035977.3	Q68DX3-4
FRMPD2	XM_017015744.2 link	c.635G>A	p.Cys212Tyr	missense_variant	Exon 5 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.3779G>A	p.Cys1260Tyr	missense_variant	Exon 28 of 29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

145500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000263

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:

0.0000450

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000582

AC:

AN:

51546

AF XY:

0.0000387

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000619

AC:

AN:

872974

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

457650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21394

American (AMR)

AF:

0.00

AC:

AN:

43956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22274

East Asian (EAS)

AF:

0.00

AC:

AN:

36812

South Asian (SAS)

AF:

0.00

AC:

AN:

73876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2994

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

577766

Other (OTH)

AF:

0.0000736

AC:

AN:

40740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

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:

0.0000275

AC:

AN:

145500

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70780

show subpopulations

African (AFR)

AF:

0.0000263

AC:

AN:

38094

American (AMR)

AF:

0.00

AC:

AN:

14556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

5040

South Asian (SAS)

AF:

0.00

AC:

AN:

4560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

66632

Other (OTH)

AF:

0.00

AC:

AN:

1970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3779G>A (p.C1260Y) alteration is located in exon 28 (coding exon 28) of the FRMPD2 gene. This alteration results from a G to A substitution at nucleotide position 3779, causing the cysteine (C) at amino acid position 1260 to be replaced by a tyrosine (Y). 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

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.030

T;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

.;N;.

PhyloP100

1.3

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.5

.;D;D

REVEL

Benign

0.024

Sift

Benign

0.39

.;T;T

Sift4G

Benign

0.46

.;T;T

Polyphen

0.0060, 0.0040

.;B;B

Vest4

0.22, 0.18

MVP

0.25

MPC

2.5

ClinPred

0.037

GERP RS

1.9

Varity_R

0.081

gMVP

0.17

Mutation Taster

=96/4

polymorphism

(source)

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

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

chr10-48163430-C-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