chr14-24132326-C-A

Variant summary

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

The NM_203402.3(FITM1):​c.382C>A​(p.Leu128Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

FITM1
NM_203402.3 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02
Variant links:
Genes affected
FITM1 (HGNC:33714): (fat storage inducing transmembrane protein 1) Predicted to enable diacylglycerol binding activity and triglyceride binding activity. Predicted to be involved in lipid droplet formation; phospholipid biosynthetic process; and positive regulation of sequestering of triglyceride. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
FITM1NM_203402.3 linkc.382C>A p.Leu128Met missense_variant Exon 2 of 2 ENST00000267426.6 NP_981947.1 A5D6W6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FITM1ENST00000267426.6 linkc.382C>A p.Leu128Met missense_variant Exon 2 of 2 1 NM_203402.3 ENSP00000267426.5 A5D6W6-1
FITM1ENST00000559294 linkc.-207C>A 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 1 ENSP00000453741.1 A5D6W6-2
FITM1ENST00000559294 linkc.-207C>A 5_prime_UTR_variant Exon 1 of 1 ENSP00000453741.1 A5D6W6-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461766
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.382C>A (p.L128M) alteration is located in exon 2 (coding exon 2) of the FITM1 gene. This alteration results from a C to A substitution at nucleotide position 382, causing the leucine (L) at amino acid position 128 to be replaced by a methionine (M). 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
0.31
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.098
T
Eigen
Uncertain
0.22
Eigen_PC
Benign
0.16
FATHMM_MKL
Benign
0.33
N
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
1.5
L
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.20
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.030
D
Polyphen
1.0
D
Vest4
0.53
MutPred
0.70
Gain of catalytic residue at V130 (P = 0.0014);
MVP
0.60
MPC
0.49
ClinPred
0.82
D
GERP RS
4.5
Varity_R
0.20
gMVP
0.56

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1206594563; hg19: chr14-24601535; API