chr20-3862384-A-G

Position:

• chr20-3862384-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020746.5(MAVS):​c.596A>G​(p.Asp199Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

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 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=0.18046439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAVS	NM_020746.5	c.596A>G	p.Asp199Gly	missense_variant	5/7	ENST00000428216.4
MAVS	NM_001206491.2	c.173A>G	p.Asp58Gly	missense_variant	4/6
MAVS	NM_001385663.1	c.173A>G	p.Asp58Gly	missense_variant	6/8
MAVS	NR_037921.2	n.560A>G		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4	c.596A>G	p.Asp199Gly	missense_variant	5/7	1	NM_020746.5	P1
MAVS	ENST00000416600.6	c.173A>G	p.Asp58Gly	missense_variant	4/6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2023

The c.596A>G (p.D199G) alteration is located in exon 5 (coding exon 4) of the MAVS gene. This alteration results from a A to G substitution at nucleotide position 596, causing the aspartic acid (D) at amino acid position 199 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	0.085
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.5	D;N
REVEL	Benign	0.044
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.069	T;T
Polyphen		0.99	.;D
Vest4		0.22
MutPred		0.14		.;Gain of glycosylation at T200 (P = 0.1343);
MVP		0.66
MPC		0.46
ClinPred		0.91	D
GERP RS		3.0
Varity_R		0.11
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-3843031;