rs11908032

chr20-3857752-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020746.5(MAVS):c.235T>A(p.Cys79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 1,614,206 control chromosomes in the GnomAD database, including 630 homozygotes. In-silico tool predicts a benign outcome for this variant. 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: 𝑓 0.036 (325 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (305 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003242582).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAVS	NM_020746.5	c.235T>A	p.Cys79Ser	missense_variant	3/7	ENST00000428216.4
MAVS	NM_001385663.1	c.-313T>A		5_prime_UTR_variant	3/8
MAVS	NM_001206491.2	c.-132+3011T>A		intron_variant
MAVS	NR_037921.2	n.372T>A		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4	c.235T>A	p.Cys79Ser	missense_variant	3/7	1	NM_020746.5	P1
MAVS	ENST00000416600.6	c.-132+3011T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5544 AN: 152200 Hom.: 324 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.00971 AC: 2442 AN: 251480 Hom.: 143 AF XY: 0.00686 AC XY: 932 AN XY: 135916

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.00700

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.000527

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00389 AC: 5685 AN: 1461888 Hom.: 305 Cov.: 32 AF XY: 0.00339 AC XY: 2463 AN XY: 727242

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00789

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.000248

Gnomad4 OTH exome AF: 0.00856

GnomAD4 genome AF: 0.0364 AC: 5549 AN: 152318 Hom.: 325 Cov.: 33 AF XY: 0.0346 AC XY: 2574 AN XY: 74494

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0110 Hom.: 31

Bravo AF: 0.0423

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0115 AC: 1400

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Uncertain	-0.010
Cadd	Benign	21
Dann	Benign	0.94
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.26
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);
MPC		0.22
ClinPred		0.11	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
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: rs11908032; hg19: chr20-3838399;