Variant 9-37729773-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014907.3(FRMPD1):c.658G>A(p.Glu220Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

FRMPD1
NM_014907.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62

Variant links:

Genes affected

FRMPD1 (HGNC:29159): (FERM and PDZ domain containing 1) Involved in establishment of protein localization to membrane and regulation of G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of protein-containing complex. Colocalizes with cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

FRMPD1 links:

ENSG00000255872 (HGNC:):

ENSG00000255872 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD1	NM_014907.3 linkuse as main transcript	c.658G>A	p.Glu220Lys	missense_variant	8/16	ENST00000377765.8	NP_055722.2	Q5SYB0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FRMPD1	ENST00000377765.8 linkuse as main transcript	c.658G>A	p.Glu220Lys	missense_variant	8/16	1	NM_014907.3	ENSP00000366995.3	Q5SYB0-1
FRMPD1	ENST00000539465.5 linkuse as main transcript	c.658G>A	p.Glu220Lys	missense_variant	8/16	1		ENSP00000444411.1	Q5SYB0-1
ENSG00000255872	ENST00000540557.1 linkuse as main transcript	n.*911-1745C>T		intron_variant		5		ENSP00000457548.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152160

Hom.:

Cov.:

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251320

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

106

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Feb 07, 2023

The c.658G>A (p.E220K) alteration is located in exon 8 (coding exon 7) of the FRMPD1 gene. This alteration results from a G to A substitution at nucleotide position 658, causing the glutamic acid (E) at amino acid position 220 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.049

T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

.;D

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Uncertain

0.29

MutationAssessor

Uncertain

2.9

M;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.6

D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

1.0

D;D

Vest4

0.57

MVP

0.93

MPC

0.58

ClinPred

0.83

GERP RS

5.6

Varity_R

0.44

gMVP

0.54

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