Genetic Variant MAVS:p.Cys79Ser (chr20-3857752-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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.

Frequency

Genomes: 𝑓 0.036 ( 325 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 305 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40

Publications

6 publications found

Variant links:

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]

MAVS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAVS	NM_020746.5	MANE Select	c.235T>A	p.Cys79Ser	missense	Exon 3 of 7	NP_065797.2	Q7Z434-1
MAVS	NM_001385663.1		c.-313T>A		5_prime_UTR	Exon 3 of 8	NP_001372592.1	Q7Z434-4
MAVS	NM_001206491.2		c.-132+3011T>A		intron	N/A	NP_001193420.1	Q7Z434-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAVS	ENST00000428216.4	TSL:1 MANE Select	c.235T>A	p.Cys79Ser	missense	Exon 3 of 7	ENSP00000401980.2	Q7Z434-1
MAVS	ENST00000416600.6	TSL:1	c.-132+3011T>A		intron	N/A	ENSP00000413749.2	Q7Z434-4
MAVS	ENST00000883971.1		c.235T>A	p.Cys79Ser	missense	Exon 2 of 6	ENSP00000554030.1

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5544

AN:

152200

Hom.:

324

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00971

AC:

2442

AN:

251480

AF XY:

0.00686

show subpopulations

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 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.:

AF XY:

0.00339

AC XY:

2463

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.133

AC:

4445

AN:

33478

American (AMR)

AF:

0.00789

AC:

353

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000243

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000693

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000248

AC:

276

AN:

1112010

Other (OTH)

AF:

0.00856

AC:

517

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

297

595

892

1190

1487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0364

AC:

5549

AN:

152318

Hom.:

325

Cov.:

AF XY:

0.0346

AC XY:

2574

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.126

AC:

5226

AN:

41538

American (AMR)

AF:

0.0135

AC:

206

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68034

Other (OTH)

AF:

0.0350

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

238

475

713

950

1188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.0423

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0115

AC:

1400

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.1

PhyloP100

3.4

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.3

REVEL

Benign

0.26

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.26

MutPred

0.18

Gain of disorder (P = 0.0506)

MPC

0.22

ClinPred

0.11

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.46

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over