9-27524617-C-A

Position:

• chr9-27524617-C-A

Variant summary

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

The NM_020124.3(IFNK):​c.281C>A​(p.Ala94Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFNK NM_020124.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

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]

ACMG classification

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	UniProt
IFNK	NM_020124.3	c.281C>A	p.Ala94Asp	missense_variant	1/2	ENST00000276943.3
MOB3B	NM_024761.5	c.-199+4938G>T		intron_variant		ENST00000262244.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNK	ENST00000276943.3	c.281C>A	p.Ala94Asp	missense_variant	1/2	1	NM_020124.3	P1
MOB3B	ENST00000262244.6	c.-199+4938G>T		intron_variant		1	NM_024761.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461814 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727198

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.16	T
Polyphen		0.56	P
Vest4		0.66
MutPred		0.66		Loss of MoRF binding (P = 0.0662);
MVP		0.48
MPC		0.020
ClinPred		0.86	D
GERP RS		2.7
Varity_R		0.63
gMVP		0.60

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

Other links and lift over

dbSNP: rs113025728; hg19: chr9-27524615;