Variant 10-48171029-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001018071.4(FRMPD2):c.3403G>A(p.Val1135Met) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000044 ( 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: 5.09

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FRMPD2	NM_001018071.4 linkuse as main transcript	c.3403G>A	p.Val1135Met	missense_variant	26/29	ENST00000374201.8
FRMPD2	NM_001318191.1 linkuse as main transcript	c.3328G>A	p.Val1110Met	missense_variant	24/27
FRMPD2	NM_001042512.3 linkuse as main transcript	c.436G>A	p.Val146Met	missense_variant	3/6
FRMPD2	XM_017015744.2 linkuse as main transcript	c.259G>A	p.Val87Met	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD2	ENST00000374201.8 linkuse as main transcript	c.3403G>A	p.Val1135Met	missense_variant	26/29	1	NM_001018071.4	P2	Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145044

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000348

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:

0.0000458

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000801

AC:

AN:

37466

Hom.:

AF XY:

0.0000522

AC XY:

AN XY:

19168

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:

0.000409

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000836

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000439

AC:

AN:

705396

Hom.:

Cov.:

AF XY:

0.0000398

AC XY:

AN XY:

377310

show subpopulations

Gnomad4 AFR exome

AF:

0.000146

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000555

Gnomad4 SAS exome

AF:

0.0000855

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000377

Gnomad4 OTH exome

AF:

0.0000567

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000131

AC:

AN:

145160

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

70186

show subpopulations

Gnomad4 AFR

AF:

0.000273

Gnomad4 AMR

AF:

0.000348

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000458

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000125

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

May 13, 2024

The c.3403G>A (p.V1135M) alteration is located in exon 26 (coding exon 26) of the FRMPD2 gene. This alteration results from a G to A substitution at nucleotide position 3403, causing the valine (V) at amino acid position 1135 to be replaced by a methionine (M). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.1

.;M;.

MutationTaster

Benign

0.76

N;N;N;N

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.7

.;D;D

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

.;D;D

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

1.0

.;D;D

Vest4

0.68, 0.70

MVP

0.44

MPC

3.1

ClinPred

0.76

GERP RS

3.3

Varity_R

0.42

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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