Variant 9-21206883-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002171.2(IFNA10):c.215A>G(p.Gln72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

IFNA10
NM_002171.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.536

Variant links:

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]

IFNA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23036033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNA10	NM_002171.2 linkuse as main transcript	c.215A>G	p.Gln72Arg	missense_variant	1/1	ENST00000357374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNA10	ENST00000357374.2 linkuse as main transcript	c.215A>G	p.Gln72Arg	missense_variant	1/1		NM_002171.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251020

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000123

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000591

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.215A>G (p.Q72R) alteration is located in exon 1 (coding exon 1) of the IFNA10 gene. This alteration results from a A to G substitution at nucleotide position 215, causing the glutamine (Q) at amino acid position 72 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.80

M_CAP

Benign

0.0027

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.089

Sift

Uncertain

0.014

Sift4G

Benign

0.10

Polyphen

0.0010

Vest4

0.099

MutPred

0.84

Loss of ubiquitination at K73 (P = 0.063);

MVP

0.27

MPC

0.12

ClinPred

0.28

GERP RS

2.6

Varity_R

0.25

gMVP

0.37

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over