chr20-3865828-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_020746.5(MAVS):​c.1304G>T​(p.Cys435Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (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 Uncertain_significance. 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=0.19527084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.1304G>T	p.Cys435Phe	missense_variant	Exon 7 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.881G>T	p.Cys294Phe	missense_variant	Exon 6 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.881G>T	p.Cys294Phe	missense_variant	Exon 8 of 8		NP_001372592.1
MAVS	NR_037921.2	n.1268G>T		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>T	p.Cys435Phe	missense_variant	Exon 7 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.881G>T	p.Cys294Phe	missense_variant	Exon 6 of 6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	.;D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-9.4	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	.;D
Vest4		0.46
MutPred		0.43		.;Gain of phosphorylation at S430 (P = 0.1853);
MVP		0.78
MPC		0.76
ClinPred		1.0	D
GERP RS		2.4
Varity_R		0.51
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3846475;