chr9-21206701-G-C

Variant names:

• chr9-21206701-G-C
• rs1587907631
• NM_002171.2:c.397C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002171.2(IFNA10):​c.397C>G​(p.Pro133Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P133H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFNA10 NM_002171.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.904
• Publications: 0 publications found

Genes affected

IFNA10 (HGNC:5418): (interferon alpha 10) This gene encodes a protein that belongs to the type I interferon family of proteins, and is located in a cluster of alpha interferon genes on chromosome 9. Interferons are small regulatory molecules that function in cell signaling in response to viruses and other pathogens or tumor cells. This gene is intronless and the encoded protein is secreted. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07704449).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002171.2. 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
	IFNA10	NM_002171.2	MANE Select	c.397C>G	p.Pro133Ala	missense	Exon 1 of 1	NP_002162.1	P01566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA10	ENST00000357374.2	TSL:6 MANE Select	c.397C>G	p.Pro133Ala	missense	Exon 1 of 1	ENSP00000369566.1	P01566

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151820 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461802 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151820 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74156

African (AFR) AF: 0.00 AC: 0 AN: 41182

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

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	0.081
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.035
DANN	Benign	0.46
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.92	L
PhyloP100		-0.90
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.030
Sift	Benign	0.18	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.087
MutPred		0.47		Loss of disorder (P = 0.1)
MVP		0.081
MPC		0.089
ClinPred		0.19	T
GERP RS		-7.5
PromoterAI		0.021	Neutral
Varity_R		0.040
gMVP		0.030
Mutation Taster		=100/0	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

dbSNP: rs1587907631; hg19: chr9-21206700;