Variant rs41303149 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001368397.1(FRMPD4):c.3937C>A(p.Arg1313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,198,771 control chromosomes in the GnomAD database, including 8 homozygotes. There are 742 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 0.0015 ( 0 hom., 46 hem., cov: 23)

Exomes 𝑓: 0.0020 ( 8 hom. 696 hem. )

Consequence

FRMPD4
NM_001368397.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 2.60

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant X-12718763-C-A is Benign according to our data. Variant chrX-12718763-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 167103.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=2}. Variant chrX-12718763-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.6 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 46 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1 linkuse as main transcript	c.3937C>A	p.Arg1313=	synonymous_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.3937C>A	p.Arg1313=	synonymous_variant	16/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

165

AN:

111968

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

AN XY:

34140

show subpopulations

Gnomad AFR

AF:

0.000227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000941

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00447

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00184

AC:

330

AN:

179217

Hom.:

AF XY:

0.00176

AC XY:

115

AN XY:

65499

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.000137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00107

Gnomad FIN exome

AF:

0.00526

Gnomad NFE exome

AF:

0.00263

Gnomad OTH exome

AF:

0.00225

GnomAD4 exome

AF:

0.00195

AC:

2123

AN:

1086750

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

696

AN XY:

352788

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.000207

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00430

Gnomad4 NFE exome

AF:

0.00216

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00147

AC:

165

AN:

112021

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

34203

show subpopulations

Gnomad4 AFR

AF:

0.000227

Gnomad4 AMR

AF:

0.0000939

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00447

Gnomad4 NFE

AF:

0.00244

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00126

EpiCase

AF:

0.00175

EpiControl

AF:

0.00166

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 20, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 29, 2015

- -

Autism, susceptibility to, X-linked 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

9.7

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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