20-3857753-G-C

Position:

• chr20-3857753-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C79F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAVS	NM_020746.5	c.236G>C	p.Cys79Ser	missense_variant	3/7	ENST00000428216.4
MAVS	NM_001385663.1	c.-312G>C		5_prime_UTR_variant	3/8
MAVS	NM_001206491.2	c.-132+3012G>C		intron_variant
MAVS	NR_037921.2	n.373G>C		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4	c.236G>C	p.Cys79Ser	missense_variant	3/7	1	NM_020746.5	P1
MAVS	ENST00000416600.6	c.-132+3012G>C		intron_variant		1

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
MutationTaster	Benign	0.98	D;D;D
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

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: rs11905552; hg19: chr20-3838400;