1-78628271-C-A

Variant summary

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

The NM_006820.4(IFI44L):​c.356C>A​(p.Thr119Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

IFI44L
NM_006820.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.42
Variant links:
Genes affected
IFI44L (HGNC:17817): (interferon induced protein 44 like) Predicted to enable GTP binding activity. Involved in defense response to virus. Predicted to be located in cytoplasm. [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=0.0461573).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFI44LNM_006820.4 linkc.356C>A p.Thr119Lys missense_variant Exon 2 of 9 ENST00000370751.10 NP_006811.2 Q53G44-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFI44LENST00000370751.10 linkc.356C>A p.Thr119Lys missense_variant Exon 2 of 9 1 NM_006820.4 ENSP00000359787.4 Q53G44-1
IFI44LENST00000459784.6 linkc.-296-680C>A intron_variant Intron 2 of 8 3 ENSP00000506096.1 B4E019

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151920
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248756
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134600
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.00
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
Cov.:
32
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151920
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74156
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.356C>A (p.T119K) alteration is located in exon 2 (coding exon 1) of the IFI44L gene. This alteration results from a C to A substitution at nucleotide position 356, causing the threonine (T) at amino acid position 119 to be replaced by a lysine (K). 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
0.087
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.0010
DANN
Benign
0.18
DEOGEN2
Benign
0.0012
T;.
Eigen
Benign
-2.3
Eigen_PC
Benign
-2.4
FATHMM_MKL
Benign
0.0055
N
LIST_S2
Benign
0.28
T;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.046
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.19
N;N
REVEL
Benign
0.017
Sift
Benign
0.92
T;T
Sift4G
Benign
0.91
T;T
Polyphen
0.0
B;.
Vest4
0.11
MutPred
0.57
Gain of solvent accessibility (P = 0.0038);.;
MVP
0.040
MPC
0.013
ClinPred
0.019
T
GERP RS
-7.2
Varity_R
0.034
gMVP
0.16

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: rs77163359; hg19: chr1-79093956; API