Variant 9-21367866-A-G 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_006900.4(IFNA13):c.145T>C(p.Ser49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,608,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

IFNA13
NM_006900.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.781

Variant links:

Genes affected

IFNA13 (HGNC:5419): (interferon alpha 13) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IFNA13 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=0.19139653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA13	NM_006900.4 linkuse as main transcript	c.145T>C	p.Ser49Pro	missense_variant	1/1	ENST00000610660.2	NP_008831.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA13	ENST00000610660.2 linkuse as main transcript	c.145T>C	p.Ser49Pro	missense_variant	1/1		NM_006900.4	ENSP00000480467	P4
IFNA13	ENST00000449498.2 linkuse as main transcript	c.142T>C	p.Ser48Pro	missense_variant	1/1			ENSP00000394494	A1

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

148238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000193

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

247628

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134230

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000232

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000116

AC:

170

AN:

1460274

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

726370

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000145

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000108

AC:

AN:

148238

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

72130

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000672

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000195

Gnomad4 NFE

AF:

0.000193

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000192

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000140

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

Feb 27, 2024

The c.145T>C (p.S49P) alteration is located in exon 1 (coding exon 1) of the IFNA13 gene. This alteration results from a T to C substitution at nucleotide position 145, causing the serine (S) at amino acid position 49 to be replaced by a proline (P). 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

0.096

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

REVEL

Benign

0.043

Sift4G

Benign

0.26

T;T

Vest4

0.21

MutPred

0.76

.;Loss of phosphorylation at S49 (P = 0.0249);

MVP

0.068

MPC

1.8

ClinPred

0.066

GERP RS

1.4

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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