Variant 9-37707451-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014907.3(FRMPD1):c.137A>T(p.Asn46Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

FRMPD1
NM_014907.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0790

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026046604).

BP6

Variant 9-37707451-A-T is Benign according to our data. Variant chr9-37707451-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2349384.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD1	NM_014907.3 linkuse as main transcript	c.137A>T	p.Asn46Ile	missense_variant	3/16	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.137A>T	p.Asn46Ile	missense_variant	3/16	1	NM_014907.3	ENSP00000366995.3	Q5SYB0-1
FRMPD1	ENST00000539465.5 linkuse as main transcript	c.137A>T	p.Asn46Ile	missense_variant	3/16	1		ENSP00000444411.1	Q5SYB0-1
ENSG00000255872	ENST00000540557.1 linkuse as main transcript	n.*1012-14186T>A		intron_variant		5		ENSP00000457548.1
FRMPD1	ENST00000359927.3 linkuse as main transcript	c.137A>T	p.Asn46Ile	missense_variant	3/3	3		ENSP00000439868.1	F5H0G3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251188

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

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:

0.000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000269

AC:

393

AN:

1461804

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

186

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

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:

0.000340

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000138

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000317

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.92

DEOGEN2

Benign

0.0029

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.51

.;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.49

N;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.74

N;N;D

REVEL

Benign

0.035

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.094

MVP

0.14

MPC

0.18

ClinPred

0.026

GERP RS

-1.8

Varity_R

0.085

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