17-43013574-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330230.2(IFI35):​c.474C>G​(p.Phe158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. F158Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

IFI35
NM_001330230.2 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70
Variant links:
Genes affected
IFI35 (HGNC:5399): (interferon induced protein 35) Enables identical protein binding activity. Involved in several processes, including macrophage activation involved in immune response; positive regulation of defense response; and regulation of signal transduction. Located in several cellular components, including cytosol; extracellular space; and nucleus. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30760753).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFI35NM_001330230.2 linkc.474C>G p.Phe158Leu missense_variant Exon 5 of 7 ENST00000415816.7 NP_001317159.1 P80217-1
IFI35NM_005533.5 linkc.480C>G p.Phe160Leu missense_variant Exon 5 of 7 NP_005524.2 P80217-2
IFI35XM_017024584.2 linkc.420C>G p.Phe140Leu missense_variant Exon 5 of 7 XP_016880073.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFI35ENST00000415816.7 linkc.474C>G p.Phe158Leu missense_variant Exon 5 of 7 5 NM_001330230.2 ENSP00000394579.3 P80217-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251188
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000870
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461874
Hom.:
0
Cov.:
39
AF XY:
0.0000344
AC XY:
25
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000554
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000596
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00154
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00143
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.480C>G (p.F160L) alteration is located in exon 5 (coding exon 5) of the IFI35 gene. This alteration results from a C to G substitution at nucleotide position 480, causing the phenylalanine (F) at amino acid position 160 to be replaced by a leucine (L). 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
Pathogenic
0.97
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.23
Sift
Benign
0.081
T;T
Sift4G
Benign
0.15
T;T
Polyphen
1.0
D;.
Vest4
0.64
MutPred
0.57
Gain of ubiquitination at K154 (P = 0.0945);.;
MVP
0.29
MPC
0.43
ClinPred
0.22
T
GERP RS
4.0
Varity_R
0.44
gMVP
0.62

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: rs769757979; hg19: chr17-41165591; API