14-24131619-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203402.3(FITM1):​c.56C>T​(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,610,636 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

FITM1
NM_203402.3 missense

Scores

1
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.492
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 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=0.01075986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FITM1NM_203402.3 linkc.56C>T p.Ala19Val missense_variant Exon 1 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.56C>T p.Ala19Val missense_variant Exon 1 of 2 1 NM_203402.3 ENSP00000267426.5 A5D6W6-1
ENSG00000259371ENST00000558325.2 linkc.638C>T p.Ala213Val missense_variant Exon 4 of 4 5 ENSP00000453089.2 H0YL77

Frequencies

GnomAD3 genomes
AF:
0.000480
AC:
73
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000779
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000529
AC:
129
AN:
244002
Hom.:
0
AF XY:
0.000482
AC XY:
64
AN XY:
132744
show subpopulations
Gnomad AFR exome
AF:
0.0000642
Gnomad AMR exome
AF:
0.000233
Gnomad ASJ exome
AF:
0.00133
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000191
Gnomad NFE exome
AF:
0.000910
Gnomad OTH exome
AF:
0.000670
GnomAD4 exome
AF:
0.000610
AC:
889
AN:
1458312
Hom.:
1
Cov.:
34
AF XY:
0.000615
AC XY:
446
AN XY:
725166
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000247
Gnomad4 ASJ exome
AF:
0.00135
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000152
Gnomad4 NFE exome
AF:
0.000726
Gnomad4 OTH exome
AF:
0.000415
GnomAD4 genome
AF:
0.000479
AC:
73
AN:
152324
Hom.:
0
Cov.:
33
AF XY:
0.000456
AC XY:
34
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000779
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000723
Hom.:
0
Bravo
AF:
0.000393
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000585
AC:
71
EpiCase
AF:
0.00153
EpiControl
AF:
0.000772

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 16, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.56C>T (p.A19V) alteration is located in exon 1 (coding exon 1) of the FITM1 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the alanine (A) at amino acid position 19 to be replaced by a valine (V). 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
0.10
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
13
DANN
Benign
0.97
DEOGEN2
Benign
0.043
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.045
N
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.014
Sift
Benign
0.20
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.0
B
Vest4
0.12
MVP
0.22
MPC
0.17
ClinPred
0.014
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.043
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs147792464; hg19: chr14-24600828; API