chr6-75312617-C-G

Variant summary

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

The NM_015687.5(FILIP1):ā€‹c.3215G>Cā€‹(p.Gly1072Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

FILIP1
NM_015687.5 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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]

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
FILIP1NM_015687.5 linkuse as main transcriptc.3215G>C p.Gly1072Ala missense_variant 5/6 ENST00000237172.12 NP_056502.1 Q7Z7B0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FILIP1ENST00000237172.12 linkuse as main transcriptc.3215G>C p.Gly1072Ala missense_variant 5/61 NM_015687.5 ENSP00000237172.7 Q7Z7B0-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152070
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251456
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461882
Hom.:
0
Cov.:
35
AF XY:
0.00000963
AC XY:
7
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152070
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.000193
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

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 GeneticsOct 24, 2024The c.3215G>C (p.G1072A) alteration is located in exon 5 (coding exon 4) of the FILIP1 gene. This alteration results from a G to C substitution at nucleotide position 3215, causing the glycine (G) at amino acid position 1072 to be replaced by an alanine (A). 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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;T;T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.64
D;D;D
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.5
M;M;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.5
D;N;N
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.98
D;D;.
Vest4
0.83
MVP
0.90
MPC
0.63
ClinPred
0.77
D
GERP RS
5.6
Varity_R
0.53
gMVP
0.91

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: rs375230665; hg19: chr6-76022333; API