NM_020746.5:c.1301G>C

Variant names:

• chr20-3865825-G-C
• rs1200742851
• NM_020746.5:c.1301G>C

Variant summary

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

The NM_020746.5(MAVS):​c.1301G>C​(p.Gly434Ala) 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. 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)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07907295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.1301G>C	p.Gly434Ala	missense_variant	Exon 7 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.878G>C	p.Gly293Ala	missense_variant	Exon 6 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.878G>C	p.Gly293Ala	missense_variant	Exon 8 of 8		NP_001372592.1
MAVS	NR_037921.2	n.1265G>C		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.1301G>C	p.Gly434Ala	missense_variant	Exon 7 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.878G>C	p.Gly293Ala	missense_variant	Exon 6 of 6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.6
DANN	Benign	0.43
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D;N
REVEL	Benign	0.093
Sift	Benign	0.57	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.54	.;P
Vest4		0.11
MutPred		0.11		.;Loss of glycosylation at S433 (P = 0.0458);
MVP		0.49
MPC		0.35
ClinPred		0.33	T
GERP RS		-1.5
Varity_R		0.14
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs1200742851; hg19: chr20-3846472;