rs759340726

Variant summary

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

The NM_021034.3(IFITM3):ā€‹c.367G>Cā€‹(p.Val123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

IFITM3
NM_021034.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.27
Variant links:
Genes affected
IFITM3 (HGNC:5414): (interferon induced transmembrane protein 3) Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2. [provided by RefSeq, Nov 2021]

Genome browser will be placed here

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=0.07138339).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFITM3NM_021034.3 linkc.367G>C p.Val123Leu missense_variant Exon 2 of 2 ENST00000399808.5 NP_066362.2 Q01628

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFITM3ENST00000399808.5 linkc.367G>C p.Val123Leu missense_variant Exon 2 of 2 1 NM_021034.3 ENSP00000382707.4 Q01628

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249536
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000479
AC:
7
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727242
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:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
0.016
DANN
Benign
0.69
DEOGEN2
Benign
0.018
T;T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.17
T;.;T
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.2
L;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.97
N;N;.
REVEL
Benign
0.21
Sift
Benign
0.14
T;T;.
Sift4G
Benign
0.096
T;T;T
Polyphen
0.0060
B;.;.
Vest4
0.17
MutPred
0.34
Loss of sheet (P = 0.0126);.;.;
MVP
0.21
MPC
0.56
ClinPred
0.045
T
GERP RS
-6.1
Varity_R
0.046
gMVP
0.40

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

LitVar

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

Other links and lift over

dbSNP: rs759340726; hg19: chr11-319873; API