Variant 6-75308704-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015687.5(FILIP1):c.3629G>T(p.Gly1210Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000744 in 1,613,014 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 1 hom. )

Consequence

FILIP1
NM_015687.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

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]

FILIP1 links:

TMEM30A-DT (HGNC:48985): (TMEM30A divergent transcript)

TMEM30A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051194876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FILIP1	NM_015687.5 linkuse as main transcript	c.3629G>T	p.Gly1210Val	missense_variant	6/6	ENST00000237172.12	NP_056502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FILIP1	ENST00000237172.12 linkuse as main transcript	c.3629G>T	p.Gly1210Val	missense_variant	6/6	1	NM_015687.5	ENSP00000237172	P4	Q7Z7B0-1
TMEM30A-DT	ENST00000661161.1 linkuse as main transcript	n.297-3664C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000720

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

251266

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1460738

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000112

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000444

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Aug 16, 2022

The c.3629G>T (p.G1210V) alteration is located in exon 6 (coding exon 5) of the FILIP1 gene. This alteration results from a G to T substitution at nucleotide position 3629, causing the glycine (G) at amino acid position 1210 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0049

T;T

Eigen

Benign

0.038

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.094

Sift

Benign

0.077

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.090

B;.

Vest4

0.23

MVP

0.59

MPC

0.22

ClinPred

0.033

GERP RS

5.2

Varity_R

0.44

gMVP

0.28

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