3-99848431-C-T

Variant names:

• chr3-99848431-C-T
• rs140594225
• NM_001387850.1:c.3245G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001387850.1(FILIP1L):​c.3245G>A​(p.Ser1082Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000379 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: FILIP1L NM_001387850.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 3.69
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070993304).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.3245G>A	p.Ser1082Asn	missense	Exon 5 of 6	NP_001374779.1	H7C4M0
	CMSS1	NM_032359.4	MANE Select	c.64+30388C>T		intron	N/A	NP_115735.2	Q9BQ75-1
	FILIP1L	NM_182909.4		c.3245G>A	p.Ser1082Asn	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.3245G>A	p.Ser1082Asn	missense	Exon 5 of 6	ENSP00000417617.2	H7C4M0
	FILIP1L	ENST00000354552.7	TSL:1	c.3245G>A	p.Ser1082Asn	missense	Exon 5 of 6	ENSP00000346560.3	Q4L180-1
	FILIP1L	ENST00000331335.9	TSL:1	c.3245G>A	p.Ser1082Asn	missense	Exon 5 of 5	ENSP00000327880.5	Q4L180-2

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 301 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00680

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000529 AC: 132 AN: 249522 AF XY: 0.000458

Gnomad AFR exome AF: 0.00756

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000212 AC: 310 AN: 1461852 Hom.: 2 Cov.: 33 AF XY: 0.000186 AC XY: 135 AN XY: 727224

African (AFR) AF: 0.00768 AC: 257 AN: 33474

American (AMR) AF: 0.000470 AC: 21 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111982

Other (OTH) AF: 0.000447 AC: 27 AN: 60394

GnomAD4 genome AF: 0.00198 AC: 301 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.00185 AC XY: 138 AN XY: 74474

African (AFR) AF: 0.00678 AC: 282 AN: 41570

American (AMR) AF: 0.000654 AC: 10 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000473 Hom.: 1

Bravo AF: 0.00227

ESP6500AA AF: 0.00824 AC: 34

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000719 AC: 87

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FILIP1L-related disorder (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.018
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.061
Sift	Benign	0.87	T
Sift4G	Benign	0.50	T
Polyphen		0.012	B
Vest4		0.25
MVP		0.29
MPC		0.059
ClinPred		0.030	T
GERP RS		5.9
Varity_R		0.088
gMVP		0.50
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: rs140594225; hg19: chr3-99567275;