chr9-21206646-G-C

Variant names:

• chr9-21206646-G-C
• rs751465414
• NM_002171.2:c.452C>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.452C>G​(p.Thr151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T151I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: IFNA10 NM_002171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.37
• Publications: 1 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=0.07905632).

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.452C>G	p.Thr151Ser	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.452C>G	p.Thr151Ser	missense	Exon 1 of 1	ENSP00000369566.1	P01566

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251446 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.11
DANN	Benign	0.75
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		-4.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.050
Sift	Benign	0.18	T
Sift4G	Benign	0.55	T
Polyphen		0.0060	B
Vest4		0.053
MutPred		0.61		Gain of MoRF binding (P = 0.1099)
MVP		0.38
MPC		0.11
ClinPred		0.042	T
GERP RS		-4.2
PromoterAI		-0.0018	Neutral
Varity_R		0.069
gMVP		0.042
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751465414; hg19: chr9-21206645;