9-21207001-C-T

Variant names:

• chr9-21207001-C-T
• rs10113875
• NM_002171.2:c.97G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002171.2(IFNA10):​c.97G>A​(p.Gly33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNA10 NM_002171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04619944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA10	NM_002171.2	c.97G>A	p.Gly33Ser	missense_variant	Exon 1 of 1	ENST00000357374.2	NP_002162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA10	ENST00000357374.2	c.97G>A	p.Gly33Ser	missense_variant	Exon 1 of 1	6	NM_002171.2	ENSP00000369566.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151378 Hom.: 0 Cov.: 31

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460402 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726532

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151378 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73910

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0050
DANN	Benign	0.57
DEOGEN2	Benign	0.00044	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00096	N
LIST_S2	Benign	0.079	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.80	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.012
Sift	Benign	0.79	T
Sift4G	Benign	0.73	T
Polyphen		0.0060	B
Vest4		0.065
MutPred		0.28		Gain of disorder (P = 0.0833);
MVP		0.12
MPC		0.095
ClinPred		0.030	T
GERP RS		-4.7
Varity_R		0.073
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs10113875; hg19: chr9-21207000;