NM_006900.4:c.269A>C

Variant names:

• chr9-21367742-T-G
• rs761128431
• NM_006900.4:c.269A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006900.4(IFNA13):​c.269A>C​(p.Asn90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,312,964 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: IFNA13 NM_006900.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30044246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA13	NM_006900.4	c.269A>C	p.Asn90Thr	missense_variant	Exon 1 of 1	ENST00000610660.2	NP_008831.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA13	ENST00000610660.2	c.269A>C	p.Asn90Thr	missense_variant	Exon 1 of 1	6	NM_006900.4	ENSP00000480467.1
IFNA13	ENST00000449498.2	c.266A>C	p.Asn89Thr	missense_variant	Exon 1 of 1	6		ENSP00000394494.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000655 AC: 1 AN: 152736 Hom.: 0 AF XY: 0.0000121 AC XY: 1 AN XY: 82642

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: 0.0000527

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1312964 Hom.: 0 Cov.: 24 AF XY: 0.00000154 AC XY: 1 AN XY: 650644

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: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000882 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.84
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.37	T
REVEL	Benign	0.021
Sift4G	Benign	0.39	T;T
Vest4		0.18
MutPred		0.63		.;Loss of ubiquitination at K95 (P = 0.0896);
MVP		0.13
MPC		1.6
ClinPred		0.052	T
GERP RS		-5.1
gMVP		0.048

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

Other links and lift over

dbSNP: rs761128431; hg19: chr9-21367741;