NM_002175.2:c.62C>A

Variant names:

• chr9-21166551-G-T
• NM_002175.2:c.62C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002175.2(IFNA21):​c.62C>A​(p.Ser21Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFNA21 NM_002175.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.251
• Publications: 0 publications found

Genes affected

IFNA21 (HGNC:5424): (interferon alpha 21) This gene is a member of the alpha interferon gene cluster on the short arm of chromosome 9. Interferons are cytokines produced in response to viral infection that mediate the immune response and interfere with viral replication. The encoded protein is a type I interferon and may play a specific role in the antiviral response to rubella virus. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002175.2. 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
	IFNA21	NM_002175.2	MANE Select	c.62C>A	p.Ser21Tyr	missense	Exon 1 of 1	NP_002166.2	P01568

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA21	ENST00000380225.1	TSL:6 MANE Select	c.62C>A	p.Ser21Tyr	missense	Exon 1 of 1	ENSP00000369574.1	P01568

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.25
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.017	D
Polyphen		0.20	B
Vest4		0.38
MutPred		0.73		Gain of solvent accessibility (P = 0.0273)
MVP		0.19
MPC		0.018
ClinPred		0.63	D
GERP RS		2.1
PromoterAI		-0.0061	Neutral
Varity_R		0.43
gMVP		0.41
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr9-21166550;