9-21227694-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_021268.2(IFNA17):ā€‹c.480C>Gā€‹(p.Ser160Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

IFNA17
NM_021268.2 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.827
Variant links:
Genes affected
IFNA17 (HGNC:5422): (interferon alpha 17) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in Crimean-Congo hemorrhagic fever and sarcoidosis. [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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IFNA17NM_021268.2 linkuse as main transcriptc.480C>G p.Ser160Arg missense_variant 1/1 ENST00000413767.2 NP_067091.1 P01571A0A7R8C355

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IFNA17ENST00000413767.2 linkuse as main transcriptc.480C>G p.Ser160Arg missense_variant 1/16 NM_021268.2 ENSP00000411940.2 P01571

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152110
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000290
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:
0.0000160
AC:
4
AN:
250660
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135556
show subpopulations
Gnomad AFR exome
AF:
0.000249
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
AF:
0.00000616
AC:
9
AN:
1461780
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00
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
AF:
0.0000789
AC:
12
AN:
152110
Hom.:
0
Cov.:
31
AF XY:
0.0000808
AC XY:
6
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.000290
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
Bravo
AF:
0.0000831
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 10, 2021The c.480C>G (p.S160R) alteration is located in exon 1 (coding exon 1) of the IFNA17 gene. This alteration results from a C to G substitution at nucleotide position 480, causing the serine (S) at amino acid position 160 to be replaced by an arginine (R). 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
0.71
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T
Eigen
Benign
-0.0039
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.081
N
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0046
T
MetaRNN
Pathogenic
0.80
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.4
M
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Benign
0.18
Sift
Uncertain
0.0050
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.72
P
Vest4
0.37
MutPred
0.90
Gain of MoRF binding (P = 0.0181);
MVP
0.36
MPC
0.11
ClinPred
0.72
D
GERP RS
0.95
Varity_R
0.62
gMVP
0.46

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: rs776716617; hg19: chr9-21227693; API