Genetic Variant MAVS:p.Gln93Glu (chr20-3857794-C-G) – 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.277C>G(p.Gln93Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,613,994 control chromosomes in the GnomAD database, including 59,318 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q93R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.23 ( 4812 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54506 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.220

Publications

42 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=6.158712E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 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.277C>G	p.Gln93Glu	missense	Exon 3 of 7	NP_065797.2	Q7Z434-1
MAVS	NM_001385663.1		c.-271C>G		5_prime_UTR	Exon 3 of 8	NP_001372592.1	Q7Z434-4
MAVS	NM_001206491.2		c.-132+3053C>G		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.277C>G	p.Gln93Glu	missense	Exon 3 of 7	ENSP00000401980.2	Q7Z434-1
MAVS	ENST00000416600.6	TSL:1	c.-132+3053C>G		intron	N/A	ENSP00000413749.2	Q7Z434-4
MAVS	ENST00000883971.1		c.277C>G	p.Gln93Glu	missense	Exon 2 of 6	ENSP00000554030.1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34921

AN:

152074

Hom.:

4810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.248

GnomAD2 exomes

AF:

0.286

AC:

71842

AN:

251358

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.0988

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.574

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.265

AC:

387488

AN:

1461802

Hom.:

54506

Cov.:

AF XY:

0.267

AC XY:

194468

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0955

AC:

3197

AN:

33480

American (AMR)

AF:

0.293

AC:

13104

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

6317

AN:

26136

East Asian (EAS)

AF:

0.561

AC:

22258

AN:

39692

South Asian (SAS)

AF:

0.325

AC:

28022

AN:

86252

European-Finnish (FIN)

AF:

0.267

AC:

14235

AN:

53400

Middle Eastern (MID)

AF:

0.270

AC:

1560

AN:

5768

European-Non Finnish (NFE)

AF:

0.254

AC:

282635

AN:

1111956

Other (OTH)

AF:

0.268

AC:

16160

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17054

34108

51161

68215

85269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9608

19216

28824

38432

48040

<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:

0.229

AC:

34924

AN:

152192

Hom.:

4812

Cov.:

AF XY:

0.235

AC XY:

17469

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.103

AC:

4266

AN:

41544

American (AMR)

AF:

0.269

AC:

4113

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

859

AN:

3472

East Asian (EAS)

AF:

0.580

AC:

3000

AN:

5176

South Asian (SAS)

AF:

0.313

AC:

1509

AN:

4826

European-Finnish (FIN)

AF:

0.265

AC:

2807

AN:

10592

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17540

AN:

67986

Other (OTH)

AF:

0.245

AC:

517

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1309

2618

3928

5237

6546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.247

Hom.:

3790

Bravo

AF:

0.226

TwinsUK

AF:

0.261

AC:

968

ALSPAC

AF:

0.255

AC:

981

ESP6500AA

AF:

0.103

AC:

452

ESP6500EA

AF:

0.248

AC:

2136

ExAC

AF:

0.280

AC:

34012

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

EpiCase

AF:

0.254

EpiControl

AF:

0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.72

MetaRNN

Benign

0.000062

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

PhyloP100

-0.22

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.51

REVEL

Benign

0.031

Sift

Benign

0.079

Sift4G

Uncertain

0.050

Polyphen

0.88

Vest4

0.069

MPC

0.18

ClinPred

0.010

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.29

gMVP

0.11

Mutation Taster

=96/4

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