3-99848807-C-A

Variant names:

• chr3-99848807-C-A
• rs1410491965
• NM_001387850.1:c.2869G>T

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037181467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387850.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1L	NM_001387850.1	MANE Select	c.2869G>T	p.Val957Leu	missense	Exon 5 of 6	NP_001374779.1	H7C4M0
	CMSS1	NM_032359.4	MANE Select	c.64+30764C>A		intron	N/A	NP_115735.2	Q9BQ75-1
	FILIP1L	NM_182909.4		c.2869G>T	p.Val957Leu	missense	Exon 5 of 6	NP_878913.2	Q4L180-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1L	ENST00000477258.2	TSL:2 MANE Select	c.2869G>T	p.Val957Leu	missense	Exon 5 of 6	ENSP00000417617.2	H7C4M0
	FILIP1L	ENST00000354552.7	TSL:1	c.2869G>T	p.Val957Leu	missense	Exon 5 of 6	ENSP00000346560.3	Q4L180-1
	FILIP1L	ENST00000331335.9	TSL:1	c.2869G>T	p.Val957Leu	missense	Exon 5 of 5	ENSP00000327880.5	Q4L180-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.55
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.065
Sift	Benign	0.36	T
Sift4G	Benign	0.71	T
Polyphen		0.0030	B
Vest4		0.037
MutPred		0.080		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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1410491965; hg19: chr3-99567651;