rs770418502

Variant names:

• chr9-27524667-C-G
• rs770418502
• NM_020124.3:c.331C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-27524667-C-G
• chr9-27524667-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020124.3(IFNK):​c.331C>G​(p.Leu111Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L111F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: IFNK NM_020124.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3837888).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020124.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNK	NM_020124.3	MANE Select	c.331C>G	p.Leu111Val	missense	Exon 1 of 2	NP_064509.2	Q9P0W0
	MOB3B	NM_024761.5	MANE Select	c.-199+4888G>C		intron	N/A	NP_079037.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNK	ENST00000276943.3	TSL:1 MANE Select	c.331C>G	p.Leu111Val	missense	Exon 1 of 2	ENSP00000276943.2	Q9P0W0
	MOB3B	ENST00000262244.6	TSL:1 MANE Select	c.-199+4888G>C		intron	N/A	ENSP00000262244.5	Q86TA1
	MOB3B	ENST00000900190.1		c.-199+4888G>C		intron	N/A	ENSP00000570249.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.2
DANN	Benign	0.75
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.042
Sift	Benign	0.11	T
Sift4G	Benign	0.41	T
Polyphen		0.010	B
Vest4		0.072
MutPred		0.81		Gain of MoRF binding (P = 0.0896)
MVP		0.20
MPC		0.0078
ClinPred		0.069	T
GERP RS		-1.0
PromoterAI		0.017	Neutral
Varity_R		0.14
gMVP		0.12
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs770418502; hg19: chr9-27524665;