9-21227776-G-A

Variant summary

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

The NM_021268.2(IFNA17):​c.398C>T​(p.Pro133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IFNA17
NM_021268.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.12
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]

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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=0.120187044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IFNA17NM_021268.2 linkc.398C>T p.Pro133Leu 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 linkc.398C>T p.Pro133Leu missense_variant 1/16 NM_021268.2 ENSP00000411940.2 P01571

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461812
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsMar 29, 2022The c.398C>T (p.P133L) alteration is located in exon 1 (coding exon 1) of the IFNA17 gene. This alteration results from a C to T substitution at nucleotide position 398, causing the proline (P) at amino acid position 133 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
Benign
0.086
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.17
DANN
Benign
0.85
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0084
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-5.0
D
REVEL
Benign
0.032
Sift
Benign
0.055
T
Sift4G
Benign
0.14
T
Polyphen
0.011
B
Vest4
0.061
MutPred
0.51
Loss of disorder (P = 0.0341);
MVP
0.24
MPC
0.015
ClinPred
0.69
D
GERP RS
-0.49
Varity_R
0.071
gMVP
0.047

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-21227775; API