Variant chrX-12716641-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001368397.1(FRMPD4):c.2182G>A(p.Ala728Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,207,976 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 77 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00021 ( 0 hom. 73 hem. )

Consequence

FRMPD4
NM_001368397.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.350

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:

FRMPD4 (HGNC:):

FRMPD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026616186).

BP6

Variant X-12716641-G-A is Benign according to our data. Variant chrX-12716641-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211050.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1 linkuse as main transcript	c.2182G>A	p.Ala728Thr	missense_variant	15/17	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.2182G>A	p.Ala728Thr	missense_variant	15/17		NM_001368397.1	ENSP00000502607.1		A0A6Q8PH73

Frequencies

GnomAD3 genomes

AF:

0.0000896

AC:

AN:

111659

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33829

show subpopulations

Gnomad AFR

AF:

0.0000651

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:

0.000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000927

AC:

AN:

183415

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

67847

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:

0.000208

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000207

AC:

227

AN:

1096317

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

361705

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000258

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.0000896

AC:

AN:

111659

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33829

show subpopulations

Gnomad4 AFR

AF:

0.0000651

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:

0.000151

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Mar 04, 2015

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 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

0.062

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.025

DANN

Benign

0.88

DEOGEN2

Benign

0.022

T;T

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

0.10

N;.

REVEL

Benign

0.014

Sift

Benign

0.54

T;.

Sift4G

Benign

0.39

T;T

Polyphen

0.0010

B;.

Vest4

0.10

MutPred

0.25

Gain of glycosylation at A728 (P = 0.0158);.;

MVP

0.10

MPC

0.12

ClinPred

0.052

GERP RS

-1.8

Varity_R

0.029

gMVP

0.17

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