X-12718764-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R1313R) has been classified as Likely benign.

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:2

Conservation

PhyloP100: 6.44

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, X-linked 104
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

FRMPD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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=2}.

BS2

High Hemizygotes in GnomAdExome4 at 32 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD4	NM_001368397.1 link	c.3938G>A	p.Arg1313Gln	missense_variant	Exon 16 of 17	ENST00000675598.1	NP_001355326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD4	ENST00000675598.1 link	c.3938G>A	p.Arg1313Gln	missense_variant	Exon 16 of 17		NM_001368397.1	ENSP00000502607.1		A0A6Q8PH73

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111885

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000140

AC:

AN:

179092

AF XY:

0.000183

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 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

African (AFR)

AF:

0.0000382

AC:

AN:

26200

American (AMR)

AF:

0.0000285

AC:

AN:

35115

Ashkenazi Jewish (ASJ)

AF:

0.000156

AC:

AN:

19278

East Asian (EAS)

AF:

0.00

AC:

AN:

30148

South Asian (SAS)

AF:

0.000410

AC:

AN:

53673

European-Finnish (FIN)

AF:

0.0000746

AC:

AN:

40236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.0000373

AC:

AN:

831584

Other (OTH)

AF:

0.0000657

AC:

AN:

45661

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111885

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34077

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30769

American (AMR)

AF:

0.00

AC:

AN:

10601

Ashkenazi Jewish (ASJ)

AF:

0.000378

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3567

South Asian (SAS)

AF:

0.000382

AC:

AN:

2621

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53206

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000198

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 05, 2015

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 09, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Jun 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

6.4

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

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.

X-12718764-G-A

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