Variant 11-65394403-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031904.5(FRMD8):c.559C>T(p.Arg187Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,568,874 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

FRMD8
NM_031904.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

FRMD8 (HGNC:25462): (FERM domain containing 8) Involved in positive regulation of tumor necrosis factor production. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FRMD8 links:

FRMD8 (HGNC:):

FRMD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020881653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD8	NM_031904.5 linkuse as main transcript	c.559C>T	p.Arg187Trp	missense_variant	6/11	ENST00000317568.10	NP_114110.1	Q9BZ67-1A8K6L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD8	ENST00000317568.10 linkuse as main transcript	c.559C>T	p.Arg187Trp	missense_variant	6/11	1	NM_031904.5	ENSP00000319726.4		Q9BZ67-1

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000617

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000401

AC:

AN:

171926

Hom.:

AF XY:

0.000332

AC XY:

AN XY:

93454

show subpopulations

Gnomad AFR exome

AF:

0.000532

Gnomad AMR exome

AF:

0.000186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000760

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000775

Gnomad NFE exome

AF:

0.000743

Gnomad OTH exome

AF:

0.000851

GnomAD4 exome

AF:

0.000699

AC:

990

AN:

1416664

Hom.:

Cov.:

AF XY:

0.000623

AC XY:

437

AN XY:

701188

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.000184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000134

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.0000218

Gnomad4 NFE exome

AF:

0.000840

Gnomad4 OTH exome

AF:

0.000936

GnomAD4 genome

AF:

0.000348

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000584

Hom.:

Bravo

AF:

0.000431

ESP6500AA

AF:

0.000469

AC:

ESP6500EA

AF:

0.000598

AC:

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.559C>T (p.R187W) alteration is located in exon 6 (coding exon 5) of the FRMD8 gene. This alteration results from a C to T substitution at nucleotide position 559, causing the arginine (R) at amino acid position 187 to be replaced by a tryptophan (W). 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

0.061

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;.;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.30

T;T;T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-0.73

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.22

T;D;T;T;T

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.0020

B;.;B;.;.

Vest4

0.33

MVP

0.67

MPC

0.29

ClinPred

0.035

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.098

gMVP

0.38

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