chr20-3857753-G-C

Variant names:

• chr20-3857753-G-C
• rs11905552
• NM_020746.5:c.236G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020746.5(MAVS):​c.236G>C​(p.Cys79Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.26
• Publications: 28 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.236G>C	p.Cys79Ser	missense_variant	Exon 3 of 7	ENST00000428216.4	NP_065797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.236G>C	p.Cys79Ser	missense_variant	Exon 3 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.-132+3012G>C		intron_variant	Intron 2 of 5	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.3
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.18		Gain of disorder (P = 0.0506);
MVP		0.74
MPC		0.22
ClinPred		0.86	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.72
gMVP		0.46
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs11905552; hg19: chr20-3838400;