Variant chrX-12498716-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001368397.1(FRMPD4):c.78G>A(p.Ser26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,196,754 control chromosomes in the GnomAD database, including 3 homozygotes. There are 101 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., 41 hem., cov: 21)

Exomes 𝑓: 0.00022 ( 1 hom. 60 hem. )

Consequence

FRMPD4
NM_001368397.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.80

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant X-12498716-G-A is Benign according to our data. Variant chrX-12498716-G-A is described in ClinVar as [Benign]. Clinvar id is 735550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD4	NM_001368397.1 linkuse as main transcript	c.78G>A	p.Ser26=	synonymous_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.78G>A	p.Ser26=	synonymous_variant	2/17		NM_001368397.1	ENSP00000502607	P2

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

198

AN:

105479

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

28691

show subpopulations

Gnomad AFR

AF:

0.00609

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

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:

0.0000777

Gnomad OTH

AF:

0.000715

GnomAD3 exomes

AF:

0.000584

AC:

106

AN:

181556

Hom.:

AF XY:

0.000332

AC XY:

AN XY:

66264

show subpopulations

Gnomad AFR exome

AF:

0.00626

Gnomad AMR exome

AF:

0.000624

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000536

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.0000494

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000221

AC:

241

AN:

1091234

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

AN XY:

356972

show subpopulations

Gnomad4 AFR exome

AF:

0.00594

Gnomad4 AMR exome

AF:

0.000598

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.0000443

Gnomad4 OTH exome

AF:

0.000545

GnomAD4 genome

AF:

0.00188

AC:

198

AN:

105520

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

28742

show subpopulations

Gnomad4 AFR

AF:

0.00608

Gnomad4 AMR

AF:

0.00184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000777

Gnomad4 OTH

AF:

0.000705

Alfa

AF:

0.000781

Hom.:

Bravo

AF:

0.00229

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

4.8

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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