Variant chrX-12498772-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001368397.1(FRMPD4):c.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,034,405 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.000017 ( 0 hom. 4 hem. )

Consequence

FRMPD4
NM_001368397.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.47

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38499385).

BS2

High Hemizygotes in GnomAdExome4 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.134G>A	p.Arg45Gln	missense_variant	2/17	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.134G>A	p.Arg45Gln	missense_variant	2/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

177773

Hom.:

AF XY:

0.00

AC XY:

AN XY:

62879

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000745

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1034405

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

308521

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000668

Gnomad4 SAS exome

AF:

0.0000193

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000191

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Oct 16, 2023

The c.134G>A (p.R45Q) alteration is located in exon 2 (coding exon 2) of the FRMPD4 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 to be replaced by a glutamine (Q). 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

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.60

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.76

N;.

REVEL

Benign

0.23

Sift

Uncertain

0.019

D;.

Sift4G

Benign

0.13

T;T

Polyphen

0.048

B;.

Vest4

0.55

MutPred

0.69

Gain of glycosylation at T42 (P = 0.2071);.;

MVP

0.61

MPC

1.5

ClinPred

0.39

GERP RS

4.3

Varity_R

0.28

gMVP

0.75

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