Variant chr3-99848465-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387850.1(FILIP1L):c.3211A>T(p.Met1071Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FILIP1L
NM_001387850.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.784

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FILIP1L	NM_001387850.1 linkuse as main transcript	c.3211A>T	p.Met1071Leu	missense_variant	5/6	ENST00000477258.2
CMSS1	NM_032359.4 linkuse as main transcript	c.64+30422T>A		intron_variant		ENST00000421999.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FILIP1L	ENST00000477258.2 linkuse as main transcript	c.3211A>T	p.Met1071Leu	missense_variant	5/6	2	NM_001387850.1	P4
CMSS1	ENST00000421999.8 linkuse as main transcript	c.64+30422T>A		intron_variant		1	NM_032359.4	P1	Q9BQ75-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 18, 2023

The c.3211A>T (p.M1071L) alteration is located in exon 5 (coding exon 4) of the FILIP1L gene. This alteration results from a A to T substitution at nucleotide position 3211, causing the methionine (M) at amino acid position 1071 to be replaced by a leucine (L). 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

0.095

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.020

T;T;.;.;.;.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

T;T;T;T;T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.070

T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

.;L;.;.;.;L;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.79

N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.80

T;T;T;T;T;T;T

Sift4G

Benign

0.63

.;T;T;T;T;T;T

Polyphen

0.0010, 0.0020

.;B;.;.;.;B;.

Vest4

0.17, 0.17, 0.16, 0.15

MutPred

0.29

.;Loss of phosphorylation at Y1070 (P = 0.0848);.;.;.;Loss of phosphorylation at Y1070 (P = 0.0848);.;

MVP

0.12

MPC

0.058

ClinPred

0.053

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.081

gMVP

0.056

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over