rs376282820

Variant names:

Variant summary

Our verdict is The variant received -1 classification points (ACMG Germline Pathogenicity v2019). PM2_SupportingBP4_Moderate

The NM_020746.5(MAVS):c.40C>T (p.Arg14Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000266 (AC=43) in the gnomAD database across 1,613,766 control chromosomes, including 1 homozygote. The grpmax filtering allele frequency (95% CI) is 0.000336. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R14H: Likely_benign (ClinVar VariationId 2218084, 1 star)

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.34

Publications

3 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

new If you want to explore the variant's impact on the transcript NM_020746.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 points.

PM2

Rare in gnomAD for AR/unknown gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.000336 — borderline rare for unknown gene (threshold 0.001) — PM2 supporting.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_020746.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAVS	NM_020746.5	MANE Select	c.40C>T	p.Arg14Cys	missense	Exon 2 of 7	NP_065797.2	Q7Z434-1
MAVS	NM_001206491.2		c.-209C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001193420.1	Q7Z434-4
MAVS	NM_001385663.1		c.-508C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAVS	ENST00000416600.6	TSL:1	c.-209C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000413749.2	Q7Z434-4
MAVS	ENST00000428216.4	TSL:1 MANE Select	c.40C>T	p.Arg14Cys	missense	Exon 2 of 7	ENSP00000401980.2	Q7Z434-1
MAVS	ENST00000416600.6	TSL:1	c.-209C>T		5_prime_UTR	Exon 2 of 6	ENSP00000413749.2	Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000103

AC:

AN:

251448

AF XY:

0.0000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000492

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111914

Other (OTH)

AF:

0.0000331

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000460

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41378

American (AMR)

AF:

0.000197

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

Local populations

Turkish Variome

AF:

0.000177

AC:

AN:

5176

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.000223

AC:

AN:

8960

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.79

M_CAP

Benign

0.0052

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PhyloP100

-1.3

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.078

Sift

Benign

0.075

Sift4G

Benign

0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.23

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over