9-27524356-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020124.3(IFNK):āc.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
NM_020124.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 1.45
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]
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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 |
---|---|---|---|---|---|---|---|---|
IFNK | NM_020124.3 | c.20T>C | p.Met7Thr | missense_variant | 1/2 | ENST00000276943.3 | NP_064509.2 | |
MOB3B | NM_024761.5 | c.-199+5199A>G | intron_variant | ENST00000262244.6 | NP_079037.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IFNK | ENST00000276943.3 | c.20T>C | p.Met7Thr | missense_variant | 1/2 | 1 | NM_020124.3 | ENSP00000276943 | P1 | |
MOB3B | ENST00000262244.6 | c.-199+5199A>G | intron_variant | 1 | NM_024761.5 | ENSP00000262244 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151780Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250250Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135188
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GnomAD4 exome AF: 0.0000418 AC: 61AN: 1460606Hom.: 0 Cov.: 32 AF XY: 0.0000454 AC XY: 33AN XY: 726422
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 151780Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3AN XY: 74158
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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 submitter | clinical testing | Ambry Genetics | Aug 20, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at M7 (P = 0.0468);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at