20-3865833-G-C

Variant names:

• chr20-3865833-G-C
• rs760496524
• NM_020746.5:c.1309G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 1 publications found

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]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082808465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020746.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	NM_020746.5	MANE Select	c.1309G>C	p.Glu437Gln	missense	Exon 7 of 7	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.886G>C	p.Glu296Gln	missense	Exon 6 of 6	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.886G>C	p.Glu296Gln	missense	Exon 8 of 8	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	ENST00000428216.4	TSL:1 MANE Select	c.1309G>C	p.Glu437Gln	missense	Exon 7 of 7	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.886G>C	p.Glu296Gln	missense	Exon 6 of 6	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.1339G>C	p.Glu447Gln	missense	Exon 6 of 6	ENSP00000554030.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.18
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.054
Sift	Benign	0.12	T
Sift4G	Benign	0.44	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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs760496524; hg19: chr20-3846480;