Variant rs759503727 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001368397.1(FRMPD4):c.3938G>A(p.Arg1313Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,197,884 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000059 ( 0 hom. 32 hem. )

Consequence

FRMPD4
NM_001368397.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.44

Variant links:

Genes affected

FRMPD4 (HGNC:29007): (FERM and PDZ domain containing 4) This gene encodes a multi-domain (WW, PDZ, FERM) containing protein. Through its interaction with other proteins (such as PSD-95), it functions as a positive regulator of dendritic spine morphogenesis and density, and is required for the maintenance of excitatory synaptic transmission. [provided by RefSeq, Jan 2010]

FRMPD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14297307).

BP6

Variant X-12718764-G-A is Benign according to our data. Variant chrX-12718764-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211054.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAdExome4 at 32 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1 linkuse as main transcript	c.3938G>A	p.Arg1313Gln	missense_variant	16/17	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1 linkuse as main transcript	c.3938G>A	p.Arg1313Gln	missense_variant	16/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111885

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34077

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000382

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

179092

Hom.:

AF XY:

0.000183

AC XY:

AN XY:

65440

show subpopulations

Gnomad AFR exome

AF:

0.0000779

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000482

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.0000589

AC:

AN:

1085999

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

351965

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.000156

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000410

Gnomad4 FIN exome

AF:

0.0000746

Gnomad4 NFE exome

AF:

0.0000373

Gnomad4 OTH exome

AF:

0.0000657

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111885

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34077

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000382

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000198

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 05, 2015

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;.

MutationTaster

Benign

0.71

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.022

D;D

Polyphen

0.47

P;.

Vest4

0.33

MutPred

0.42

Gain of ubiquitination at K1318 (P = 0.0261);.;

MVP

0.62

MPC

0.16

ClinPred

0.073

GERP RS

4.7

Varity_R

0.63

gMVP

0.53

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