Variant X-12609818-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001368397.1(FRMPD4):c.256G>A(p.Val86Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,097,618 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000074 ( 0 hom. 28 hem. )

Consequence

FRMPD4
NM_001368397.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.33

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMPD4	NM_001368397.1 linkuse as main transcript	c.256G>A	p.Val86Met	missense_variant	3/17	ENST00000675598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD4	ENST00000675598.1 linkuse as main transcript	c.256G>A	p.Val86Met	missense_variant	3/17		NM_001368397.1	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183441

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67883

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:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000738

AC:

AN:

1097618

Hom.:

Cov.:

AF XY:

0.0000771

AC XY:

AN XY:

362988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000915

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.256G>A (p.V86M) alteration is located in exon 3 (coding exon 3) of the FRMPD4 gene. This alteration results from a G to A substitution at nucleotide position 256, causing the valine (V) at amino acid position 86 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Pathogenic

0.52

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.96

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;.

Sift4G

Benign

0.10

T;T

Polyphen

1.0

D;.

Vest4

0.51

MutPred

0.33

Gain of disorder (P = 0.0669);.;

MVP

0.73

MPC

2.0

ClinPred

0.45

GERP RS

5.3

Varity_R

0.44

gMVP

0.71

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