Variant 3-99848431-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001387850.1(FILIP1L):c.3245G>A(p.Ser1082Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000379 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

FILIP1L
NM_001387850.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

FILIP1L (HGNC:24589): (filamin A interacting protein 1 like) Predicted to be located in cytoplasm; membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FILIP1L links:

CMSS1 (HGNC:28666): (cms1 ribosomal small subunit homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CMSS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070993304).

BP6

Variant 3-99848431-C-T is Benign according to our data. Variant chr3-99848431-C-T is described in ClinVar as [Benign]. Clinvar id is 3045603.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FILIP1L	NM_001387850.1 linkuse as main transcript	c.3245G>A	p.Ser1082Asn	missense_variant	5/6	ENST00000477258.2
CMSS1	NM_032359.4 linkuse as main transcript	c.64+30388C>T		intron_variant		ENST00000421999.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FILIP1L	ENST00000477258.2 linkuse as main transcript	c.3245G>A	p.Ser1082Asn	missense_variant	5/6	2	NM_001387850.1	P4
CMSS1	ENST00000421999.8 linkuse as main transcript	c.64+30388C>T		intron_variant		1	NM_032359.4	P1	Q9BQ75-1

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000529

AC:

132

AN:

249522

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.00756

Gnomad AMR exome

AF:

0.000435

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000212

AC:

310

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00768

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152316

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00678

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000357

Hom.:

Bravo

AF:

0.00227

ESP6500AA

AF:

0.00824

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000719

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FILIP1L-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.021

T;T;.;.;.;.

Eigen

Benign

-0.018

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

T;T;T;T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.0071

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.47

N;N;N;N;N;N

REVEL

Benign

0.061

Sift

Benign

0.87

T;T;T;T;T;T

Polyphen

0.012, 0.021

.;B;.;.;.;B

Vest4

0.25, 0.27, 0.27, 0.21, 0.18

MVP

0.29

MPC

0.059

ClinPred

0.030

GERP RS

5.9

Varity_R

0.088

gMVP

0.50

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