14-24132362-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203402.3(FITM1):​c.418C>G​(p.Arg140Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FITM1
NM_203402.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.172
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]

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ACMG classification

Classification made for transcript

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=0.16281128).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FITM1NM_203402.3 linkc.418C>G p.Arg140Gly 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.418C>G p.Arg140Gly missense_variant Exon 2 of 2 1 NM_203402.3 ENSP00000267426.5 A5D6W6-1
FITM1ENST00000559294 linkc.-171C>G 5_prime_UTR_variant Exon 1 of 1 ENSP00000453741.1 A5D6W6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461522
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.418C>G (p.R140G) alteration is located in exon 2 (coding exon 2) of the FITM1 gene. This alteration results from a C to G substitution at nucleotide position 418, causing the arginine (R) at amino acid position 140 to be replaced by a glycine (G). 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
0.11
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
12
DANN
Benign
0.93
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.31
N
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.11
N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.19
Sift
Benign
0.34
T
Sift4G
Benign
0.41
T
Polyphen
0.74
P
Vest4
0.20
MutPred
0.45
Gain of catalytic residue at A138 (P = 0);
MVP
0.37
MPC
0.23
ClinPred
0.54
D
GERP RS
1.2
Varity_R
0.19
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr14-24601571; API