Variant 9-21367642-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006900.4(IFNA13):c.369T>G(p.Cys123Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,545,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 10/17 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 0.000028 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

IFNA13
NM_006900.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.215

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA13	NM_006900.4 linkuse as main transcript	c.369T>G	p.Cys123Trp	missense_variant	1/1	ENST00000610660.2	NP_008831.3	P01562A0A087WWS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA13	ENST00000610660.2 linkuse as main transcript	c.369T>G	p.Cys123Trp	missense_variant	1/1	6	NM_006900.4	ENSP00000480467.1		A0A087WWS6
IFNA13	ENST00000449498.2 linkuse as main transcript	c.366T>G	p.Cys122Trp	missense_variant	1/1	6		ENSP00000394494.2		P01562

Frequencies

GnomAD3 genomes

AF:

0.0000281

AC:

AN:

142258

Hom.:

Cov.:

show subpopulations

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:

0.000992

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

197782

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

106276

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:

0.00138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000755

AC:

106

AN:

1403306

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

693556

show subpopulations

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:

0.00128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000370

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.0000281

AC:

AN:

142258

Hom.:

Cov.:

AF XY:

0.0000437

AC XY:

AN XY:

68610

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000992

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000151

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

Sep 05, 2024

The c.369T>G (p.C123W) alteration is located in exon 1 (coding exon 1) of the IFNA13 gene. This alteration results from a T to G substitution at nucleotide position 369, causing the cysteine (C) at amino acid position 123 to be replaced by a tryptophan (W). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.41

REVEL

Benign

0.15

Sift4G

Pathogenic

0.0

D;D

Vest4

0.73

MutPred

0.87

.;Loss of stability (P = 0.0618);

MVP

0.082

MPC

3.0

ClinPred

0.25

GERP RS

-2.8

gMVP

0.33

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

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