NM_015687.5:c.3132G>T

Variant names:

• chr6-75312700-C-A
• rs1582320779
• NM_015687.5:c.3132G>T

Variant summary

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

The NM_015687.5(FILIP1):​c.3132G>T​(p.Gln1044His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FILIP1 NM_015687.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

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)

ACMG classification

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 rank	MANE	Protein	UniProt
FILIP1	NM_015687.5	c.3132G>T	p.Gln1044His	missense_variant	Exon 5 of 6	ENST00000237172.12	NP_056502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FILIP1	ENST00000237172.12	c.3132G>T	p.Gln1044His	missense_variant	Exon 5 of 6	1	NM_015687.5	ENSP00000237172.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3132G>T (p.Q1044H) alteration is located in exon 5 (coding exon 4) of the FILIP1 gene. This alteration results from a G to T substitution at nucleotide position 3132, causing the glutamine (Q) at amino acid position 1044 to be replaced by a histidine (H). 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	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	.;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0092	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.62
MutPred		0.18		Gain of ubiquitination at K1043 (P = 0.0773);Gain of ubiquitination at K1043 (P = 0.0773);.;
MVP		0.66
MPC		0.55
ClinPred		0.93	D
GERP RS		3.1
Varity_R		0.20
gMVP		0.82

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

Other links and lift over

dbSNP: rs1582320779; hg19: chr6-76022416;