NM_020746.5:c.1304G>A

Variant names:

• chr20-3865828-G-A
• NM_020746.5:c.1304G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PM1 PM2 BP4_Moderate BS2

The NM_020746.5(MAVS):​c.1304G>A​(p.Cys435Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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 Likely_benign. Variant got -2 ACMG points.

• PM1: In a mutagenesis_site No effect on cleavage by NS3/4A protease complex. (size 0) in uniprot entity MAVS_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20920831).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.1304G>A	p.Cys435Tyr	missense_variant	Exon 7 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.881G>A	p.Cys294Tyr	missense_variant	Exon 6 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.881G>A	p.Cys294Tyr	missense_variant	Exon 8 of 8		NP_001372592.1
MAVS	NR_037921.2	n.1268G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.1304G>A	p.Cys435Tyr	missense_variant	Exon 7 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.881G>A	p.Cys294Tyr	missense_variant	Exon 6 of 6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461696 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727156

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Uncertain	0.50	.;D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-9.1	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	.;D
Vest4		0.49
MutPred		0.47		.;Loss of disorder (P = 0.1001);
MVP		0.66
MPC		0.80
ClinPred		1.0	D
GERP RS		2.4
Varity_R		0.52
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3846475;