Variant rs144170600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001368397.1(FRMPD4):c.2599A>G(p.Asn867Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000382 in 1,206,761 control chromosomes in the GnomAD database, including 1 homozygotes. There are 220 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00040 ( 1 hom. 211 hem. )

Consequence

FRMPD4
NM_001368397.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.65

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034191012).

BP6

Variant X-12717058-A-G is Benign according to our data. Variant chrX-12717058-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-12717058-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMPD4	NM_001368397.1 linkuse as main transcript	c.2599A>G	p.Asn867Asp	missense_variant	15/17	ENST00000675598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD4	ENST00000675598.1 linkuse as main transcript	c.2599A>G	p.Asn867Asp	missense_variant	15/17		NM_001368397.1	P2

Frequencies

GnomAD3 genomes

AF:

0.000239

AC:

AN:

112828

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

AN XY:

34972

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000928

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00328

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000281

Gnomad OTH

AF:

0.000657

GnomAD3 exomes

AF:

0.000664

AC:

120

AN:

180770

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

65708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.000408

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00411

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000398

Gnomad OTH exome

AF:

0.000670

GnomAD4 exome

AF:

0.000398

AC:

435

AN:

1093882

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

211

AN XY:

359528

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.000776

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.000610

GnomAD4 genome

AF:

0.000230

AC:

AN:

112879

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

AN XY:

35033

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000927

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00292

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000281

Gnomad4 OTH

AF:

0.000649

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000906

AC:

110

EpiCase

AF:

0.000493

EpiControl

AF:

0.000653

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 16, 2015

- -

Intellectual disability, X-linked 104

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

FRMPD4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-1.1

CADD

Benign

7.8

DANN

Benign

0.28

DEOGEN2

Benign

0.026

T;T

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.50

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

1.8

N;.

REVEL

Benign

0.13

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.055

MVP

0.10

MPC

0.14

ClinPred

0.0094

GERP RS

2.3

Varity_R

0.049

gMVP

0.23

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