NM_020746.5:c.1309G>C

Variant names:

• chr20-3865833-G-C
• rs760496524
• NM_020746.5:c.1309G>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.1309G>C​(p.Glu437Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.185

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=0.082808465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.1309G>C	p.Glu437Gln	missense_variant	Exon 7 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.886G>C	p.Glu296Gln	missense_variant	Exon 6 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.886G>C	p.Glu296Gln	missense_variant	Exon 8 of 8		NP_001372592.1
MAVS	NR_037921.2	n.1273G>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.1309G>C	p.Glu437Gln	missense_variant	Exon 7 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.886G>C	p.Glu296Gln	missense_variant	Exon 6 of 6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1309G>C (p.E437Q) alteration is located in exon 7 (coding exon 6) of the MAVS gene. This alteration results from a G to C substitution at nucleotide position 1309, causing the glutamic acid (E) at amino acid position 437 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.054
Sift	Benign	0.12	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.27	.;B
Vest4		0.043
MutPred		0.16		.;Loss of disorder (P = 0.1264);
MVP		0.51
MPC		0.47
ClinPred		0.11	T
GERP RS		1.2
Varity_R		0.28
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs760496524; hg19: chr20-3846480;