rs17857295

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020746.5(MAVS):​c.277C>A​(p.Gln93Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q93E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.220
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18323004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAVSNM_020746.5 linkuse as main transcriptc.277C>A p.Gln93Lys missense_variant 3/7 ENST00000428216.4 NP_065797.2 Q7Z434-1
MAVSNM_001385663.1 linkuse as main transcriptc.-271C>A 5_prime_UTR_variant 3/8 NP_001372592.1
MAVSNM_001206491.2 linkuse as main transcriptc.-132+3053C>A intron_variant NP_001193420.1 Q7Z434-4
MAVSNR_037921.2 linkuse as main transcriptn.414C>A non_coding_transcript_exon_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAVSENST00000428216.4 linkuse as main transcriptc.277C>A p.Gln93Lys missense_variant 3/71 NM_020746.5 ENSP00000401980.2 Q7Z434-1
MAVSENST00000416600.6 linkuse as main transcriptc.-132+3053C>A intron_variant 1 ENSP00000413749.2 Q7Z434-4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251358
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461864
Hom.:
0
Cov.:
37
AF XY:
0.00000413
AC XY:
3
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00000900
Hom.:
3790
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.036
Sift
Benign
0.030
D
Sift4G
Benign
0.16
T
Polyphen
0.79
P
Vest4
0.35
MutPred
0.27
Gain of ubiquitination at Q93 (P = 0.0077);
MVP
0.40
MPC
0.23
ClinPred
0.073
T
GERP RS
2.5
Varity_R
0.38
gMVP
0.18

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17857295; hg19: chr20-3838441; API