3-99848807-C-A

Variant names:

• chr3-99848807-C-A
• NM_001387850.1:c.2869G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387850.1(FILIP1L):​c.2869G>T​(p.Val957Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: FILIP1L NM_001387850.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.552

Genes affected

FILIP1L (HGNC:24589): (filamin A interacting protein 1 like) Predicted to be located in cytoplasm; membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CMSS1 (HGNC:28666): (cms1 ribosomal small subunit homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374010 (HGNC:):

ACMG classification

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=0.037181467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FILIP1L	NM_001387850.1	c.2869G>T	p.Val957Leu	missense_variant	Exon 5 of 6	ENST00000477258.2	NP_001374779.1
CMSS1	NM_032359.4	c.64+30764C>A		intron_variant	Intron 1 of 9	ENST00000421999.8	NP_115735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FILIP1L	ENST00000477258.2	c.2869G>T	p.Val957Leu	missense_variant	Exon 5 of 6	2	NM_001387850.1	ENSP00000417617.2
CMSS1	ENST00000421999.8	c.64+30764C>A		intron_variant	Intron 1 of 9	1	NM_032359.4	ENSP00000410396.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2869G>T (p.V957L) alteration is located in exon 5 (coding exon 4) of the FILIP1L gene. This alteration results from a G to T substitution at nucleotide position 2869, causing the valine (V) at amino acid position 957 to be replaced by a leucine (L). 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	0.085
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.8
DANN	Benign	0.83
DEOGEN2	Benign	0.014	T;.;.;.;.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.81	T;T;T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.037	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.;.;.;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.46	N;N;N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.36	T;T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T;T
Polyphen		0.0030	B;.;.;.;B;.
Vest4		0.037
MutPred		0.080		Loss of methylation at K960 (P = 0.1228);.;.;.;Loss of methylation at K960 (P = 0.1228);.;
MVP		0.030
MPC		0.061
ClinPred		0.037	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.045
gMVP		0.15

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: chr3-99567651;