rs775896896

Variant names:

• chr21-44289798-C-G
• rs775896896
• NM_000383.4:c.794C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-44289798-C-G
• chr21-44289798-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000383.4(AIRE):​c.794C>G​(p.Ala265Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
• Consequence: AIRE NM_000383.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

Genes affected

AIRE (HGNC:360): (autoimmune regulator) This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]

ACMG classification

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=0.22634134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIRE	NM_000383.4	c.794C>G	p.Ala265Gly	missense_variant	Exon 6 of 14	ENST00000291582.6	NP_000374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIRE	ENST00000291582.6	c.794C>G	p.Ala265Gly	missense_variant	Exon 6 of 14	1	NM_000383.4	ENSP00000291582.5
AIRE	ENST00000527919.5	n.1527C>G		non_coding_transcript_exon_variant	Exon 6 of 14	2
AIRE	ENST00000530812.5	n.2544C>G		non_coding_transcript_exon_variant	Exon 4 of 12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	0.0067	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	3.7
DANN	Benign	0.54
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.30
Sift	Benign	0.034	D
Sift4G	Benign	0.49	T
Polyphen		0.89	P
Vest4		0.20
MutPred		0.23		Loss of stability (P = 0.073);
MVP		0.97
MPC		0.37
ClinPred		0.24	T
GERP RS		-0.52
Varity_R		0.072
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775896896; hg19: chr21-45709681;