6-75312803-A-C

Position:

• chr6-75312803-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015687.5(FILIP1):​c.3029T>G​(p.Met1010Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FILIP1 NM_015687.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21961284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FILIP1	NM_015687.5	c.3029T>G	p.Met1010Arg	missense_variant	5/6	ENST00000237172.12	NP_056502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FILIP1	ENST00000237172.12	c.3029T>G	p.Met1010Arg	missense_variant	5/6	1	NM_015687.5	ENSP00000237172	P4
TMEM30A-DT	ENST00000661161.1	n.732A>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2022

The c.3029T>G (p.M1010R) alteration is located in exon 5 (coding exon 4) of the FILIP1 gene. This alteration results from a T to G substitution at nucleotide position 3029, causing the methionine (M) at amino acid position 1010 to be replaced by an arginine (R). 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	0.63
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	.;T;T
Eigen	Benign	-0.071
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.
MutationTaster	Benign	0.81	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.050	D;T;T
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.0010	B;B;.
Vest4		0.40
MutPred		0.28		Gain of MoRF binding (P = 0.0615);Gain of MoRF binding (P = 0.0615);.;
MVP		0.38
MPC		0.27
ClinPred		0.78	D
GERP RS		4.9
Varity_R		0.51
gMVP		0.81

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.

Other links and lift over

hg19: chr6-76022519;