9-21367809-C-A

Variant names:

• chr9-21367809-C-A
• rs1460383741
• NM_006900.4:c.202G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006900.4(IFNA13):​c.202G>T​(p.Asp68Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,592,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000070 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: IFNA13 NM_006900.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.146
• Publications: 0 publications found

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]

MIR31HG (HGNC:37187): (MIR31 host gene) This gene produces a long non-coding RNA that acts as a host gene for miR-31. This transcript may be involved in cellular pluripotency and regulate the differentiation of myoblasts and other tissues. This RNA was found to interact with Polycomb repressive proteins to repression transcription of genes involves in cell senescence. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120415986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006900.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA13	NM_006900.4	MANE Select	c.202G>T	p.Asp68Tyr	missense	Exon 1 of 1	NP_008831.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA13	ENST00000610660.2	TSL:6 MANE Select	c.202G>T	p.Asp68Tyr	missense	Exon 1 of 1	ENSP00000480467.1	A0A087WWS6
	IFNA13	ENST00000449498.2	TSL:6	c.199G>T	p.Asp67Tyr	missense	Exon 1 of 1	ENSP00000394494.2	P01562
	MIR31HG	ENST00000773559.1		n.584-2721G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000700 AC: 10 AN: 142916 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000109

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: 0.0000901

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000864 AC: 2 AN: 231392 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000276 AC: 40 AN: 1449328 Hom.: 0 Cov.: 31 AF XY: 0.0000264 AC XY: 19 AN XY: 719760

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.00 AC: 0 AN: 43470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5600

European-Non Finnish (NFE) AF: 0.0000335 AC: 37 AN: 1104108

Other (OTH) AF: 0.0000335 AC: 2 AN: 59758

GnomAD4 genome AF: 0.0000700 AC: 10 AN: 142916 Hom.: 0 Cov.: 24 AF XY: 0.0000435 AC XY: 3 AN XY: 69014

African (AFR) AF: 0.000109 AC: 4 AN: 36794

American (AMR) AF: 0.00 AC: 0 AN: 14166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5016

South Asian (SAS) AF: 0.00 AC: 0 AN: 4258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000901 AC: 6 AN: 66564

Other (OTH) AF: 0.00 AC: 0 AN: 1894

Alfa AF: 0.0000959 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.97
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.15
PrimateAI	Benign	0.33	T
REVEL	Benign	0.027
Sift4G	Uncertain	0.0040	D
Vest4		0.21
MutPred		0.47		Loss of disorder (P = 0.0266)
MVP		0.043
MPC		1.8
ClinPred		0.26	T
GERP RS		-0.48
PromoterAI		0.017	Neutral
gMVP		0.13
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1460383741; hg19: chr9-21367808;