6-75312949-C-T

Variant summary

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

The NM_015687.5(FILIP1):​c.2883G>A​(p.Met961Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FILIP1
NM_015687.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
Variant links:
Genes affected
FILIP1 (HGNC:21015): (filamin A interacting protein 1) This gene encodes a filamin A binding protein. The encoded protein promotes the degradation of filamin A and may regulate cortical neuron migration and dendritic spine morphology. Mice lacking a functional copy of this gene exhibit reduced dendritic spine length and altered excitatory signaling. [provided by RefSeq, Oct 2016]
TMEM30A-DT (HGNC:48985): (TMEM30A divergent transcript)

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=0.12923229).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FILIP1NM_015687.5 linkuse as main transcriptc.2883G>A p.Met961Ile missense_variant 5/6 ENST00000237172.12 NP_056502.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FILIP1ENST00000237172.12 linkuse as main transcriptc.2883G>A p.Met961Ile missense_variant 5/61 NM_015687.5 ENSP00000237172 P4Q7Z7B0-1
TMEM30A-DTENST00000661161.1 linkuse as main transcriptn.878C>T non_coding_transcript_exon_variant 2/2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251236
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135766
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461838
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727226
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsApr 03, 2023The c.2883G>A (p.M961I) alteration is located in exon 5 (coding exon 4) of the FILIP1 gene. This alteration results from a G to A substitution at nucleotide position 2883, causing the methionine (M) at amino acid position 961 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Benign
0.0085
.;T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.026
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;.
MutationTaster
Benign
0.73
N;N;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.44
N;N;N
REVEL
Benign
0.10
Sift
Benign
0.52
T;T;T
Sift4G
Benign
0.41
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.18
MutPred
0.076
Gain of methylation at K966 (P = 0.1329);Gain of methylation at K966 (P = 0.1329);.;
MVP
0.48
MPC
0.19
ClinPred
0.15
T
GERP RS
5.8
Varity_R
0.19
gMVP
0.25

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.

Other links and lift over

dbSNP: rs1427768290; hg19: chr6-76022665; API