Genetic Variant FRMPD3:p.Thr97Ser (chrX-107533543-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001388459.1(FRMPD3):c.290C>G(p.Thr97Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000639 in 1,204,730 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000064 ( 0 hom. 19 hem. )

Consequence

FRMPD3
NM_001388459.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

FRMPD3 (HGNC:29382): (FERM and PDZ domain containing 3) This gene encodes a protein that contains a PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain at the N-terminus followed by a FERM domain. The encoded protein is involved in signal transduction. The PDZ domain is thought to function in protein-protein interactions, mainly by binding to specific C-terminal peptides of other proteins. The FERM domain is found in proteins that are localized to the plasma membrane and are associated with the cytoskeleton. [provided by RefSeq, May 2017]

FRMPD3 links:

FRMPD3-AS1 (HGNC:41239): (FRMPD3 antisense RNA 1)

FRMPD3-AS1 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 (MetaRNN=0.102440596).

BP6

Variant X-107533543-C-G is Benign according to our data. Variant chrX-107533543-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661145.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD3	NM_001388459.1 link	c.290C>G	p.Thr97Ser	missense_variant	Exon 4 of 15	ENST00000683843.1	NP_001375388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD3	ENST00000683843.1 link	c.290C>G	p.Thr97Ser	missense_variant	Exon 4 of 15		NM_001388459.1	ENSP00000507942.1		A0A804HKI5

Frequencies

GnomAD3 genomes

AF:

0.0000624

AC:

AN:

112182

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34328

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000820

AC:

AN:

170810

Hom.:

AF XY:

0.0000642

AC XY:

AN XY:

62350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000379

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:

0.000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000641

AC:

AN:

1092495

Hom.:

Cov.:

AF XY:

0.0000530

AC XY:

AN XY:

358717

show subpopulations

Gnomad4 AFR exome

AF:

0.0000761

Gnomad4 AMR exome

AF:

0.0000286

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:

0.0000787

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000624

AC:

AN:

112235

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34391

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000644

AC:

ExAC

AF:

0.0000603

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FRMPD3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.014

T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.55

N;.

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.042

Sift

Benign

0.35

T;T

Sift4G

Benign

0.077

T;T

Vest4

0.51

MutPred

0.43

Gain of disorder (P = 0.0371);.;

MVP

0.66

MPC

0.096

ClinPred

0.086

GERP RS

4.6

Varity_R

0.24

gMVP

0.27

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