20-3864379-C-A

Variant names:

• chr20-3864379-C-A
• NM_020746.5:c.749C>A

Variant summary

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

The NM_020746.5(MAVS):​c.749C>A​(p.Thr250Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

Genes affected

MAVS (HGNC:29233): (mitochondrial antiviral signaling protein) This gene encodes an intermediary protein necessary in the virus-triggered beta interferon signaling pathways. It is required for activation of transcription factors which regulate expression of beta interferon and contributes to antiviral innate immunity. [provided by RefSeq, Jul 2020]

ACMG classification

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 rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.749C>A	p.Thr250Asn	missense_variant	Exon 6 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.326C>A	p.Thr109Asn	missense_variant	Exon 5 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.326C>A	p.Thr109Asn	missense_variant	Exon 7 of 8		NP_001372592.1
MAVS	NR_037921.2	n.713C>A		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.749C>A	p.Thr250Asn	missense_variant	Exon 6 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.326C>A	p.Thr109Asn	missense_variant	Exon 5 of 6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461844 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727228

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.077	.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.1	D;N
REVEL	Benign	0.037
Sift	Benign	0.10	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.078	.;B
Vest4		0.19
MutPred		0.11		.;Loss of phosphorylation at T250 (P = 0.0183);
MVP		0.46
MPC		0.19
ClinPred		0.16	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: 45

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3845026;