9-27524356-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020124.3(IFNK):ā€‹c.20T>Cā€‹(p.Met7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,612,386 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000040 ( 0 hom., cov: 31)
Exomes š‘“: 0.000042 ( 0 hom. )

Consequence

IFNK
NM_020124.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
Genes affected
IFNK (HGNC:21714): (interferon kappa) This gene encodes a member of the type I interferon family. Type I interferons are a group of related glycoproteins that play an important role in host defenses against viral infections. This protein is expressed in keratinocytes and the gene is found on chromosome 9, adjacent to the type I interferon cluster. [provided by RefSeq, Jul 2008]
MOB3B (HGNC:23825): (MOB kinase activator 3B) The protein encoded by this gene shares similarity with the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. This gene is located on the opposite strand as the interferon kappa precursor (IFNK) gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IFNKNM_020124.3 linkuse as main transcriptc.20T>C p.Met7Thr missense_variant 1/2 ENST00000276943.3 NP_064509.2
MOB3BNM_024761.5 linkuse as main transcriptc.-199+5199A>G intron_variant ENST00000262244.6 NP_079037.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IFNKENST00000276943.3 linkuse as main transcriptc.20T>C p.Met7Thr missense_variant 1/21 NM_020124.3 ENSP00000276943 P1
MOB3BENST00000262244.6 linkuse as main transcriptc.-199+5199A>G intron_variant 1 NM_024761.5 ENSP00000262244 P1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151780
Hom.:
0
Cov.:
31
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000599
AC:
15
AN:
250250
Hom.:
0
AF XY:
0.0000740
AC XY:
10
AN XY:
135188
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000991
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000706
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000418
AC:
61
AN:
1460606
Hom.:
0
Cov.:
32
AF XY:
0.0000454
AC XY:
33
AN XY:
726422
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000405
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151780
Hom.:
0
Cov.:
31
AF XY:
0.0000405
AC XY:
3
AN XY:
74158
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 20, 2023The c.20T>C (p.M7T) alteration is located in exon 1 (coding exon 1) of the IFNK gene. This alteration results from a T to C substitution at nucleotide position 20, causing the methionine (M) at amino acid position 7 to be replaced by a threonine (T). 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
0.12
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
15
DANN
Benign
0.78
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.62
D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
0.99
N;D
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.20
Sift
Benign
0.052
T
Sift4G
Benign
0.19
T
Polyphen
0.42
B
Vest4
0.20
MutPred
0.85
Gain of catalytic residue at M7 (P = 0.0468);
MVP
0.46
MPC
0.011
ClinPred
0.067
T
GERP RS
4.2
Varity_R
0.24
gMVP
0.52

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: rs201598978; hg19: chr9-27524354; API