rs7269320

Variant names:

• chr20-3865750-C-T
• rs7269320
• NM_020746.5:c.1226C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020746.5(MAVS):​c.1226C>T​(p.Ser409Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,264 control chromosomes in the GnomAD database, including 23,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4161 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19832 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 44 publications found

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]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015271306).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	NM_020746.5	MANE Select	c.1226C>T	p.Ser409Phe	missense	Exon 7 of 7	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.803C>T	p.Ser268Phe	missense	Exon 6 of 6	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.803C>T	p.Ser268Phe	missense	Exon 8 of 8	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	ENST00000428216.4	TSL:1 MANE Select	c.1226C>T	p.Ser409Phe	missense	Exon 7 of 7	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.803C>T	p.Ser268Phe	missense	Exon 6 of 6	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.1256C>T	p.Ser419Phe	missense	Exon 6 of 6	ENSP00000554030.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31951 AN: 152004 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.212

GnomAD2 exomes AF: 0.158 AC: 39437 AN: 249996 AF XY: 0.157

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0972

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.158 AC: 230872 AN: 1461142 Hom.: 19832 Cov.: 34 AF XY: 0.159 AC XY: 115386 AN XY: 726880

African (AFR) AF: 0.379 AC: 12699 AN: 33476

American (AMR) AF: 0.108 AC: 4843 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4381 AN: 26134

East Asian (EAS) AF: 0.105 AC: 4155 AN: 39680

South Asian (SAS) AF: 0.177 AC: 15275 AN: 86252

European-Finnish (FIN) AF: 0.115 AC: 6079 AN: 52858

Middle Eastern (MID) AF: 0.209 AC: 1200 AN: 5736

European-Non Finnish (NFE) AF: 0.155 AC: 172057 AN: 1111934

Other (OTH) AF: 0.169 AC: 10183 AN: 60366

GnomAD4 genome AF: 0.210 AC: 31981 AN: 152122 Hom.: 4161 Cov.: 32 AF XY: 0.205 AC XY: 15254 AN XY: 74376

African (AFR) AF: 0.371 AC: 15393 AN: 41494

American (AMR) AF: 0.154 AC: 2351 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3468

East Asian (EAS) AF: 0.0850 AC: 439 AN: 5162

South Asian (SAS) AF: 0.180 AC: 867 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10594

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10653 AN: 67988

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.172 Hom.: 9256

Bravo AF: 0.219

TwinsUK AF: 0.162 AC: 601

ALSPAC AF: 0.137 AC: 528

ESP6500AA AF: 0.359 AC: 1581

ESP6500EA AF: 0.162 AC: 1393

ExAC AF: 0.164 AC: 19860

Asia WGS AF: 0.146 AC: 509 AN: 3478

EpiCase AF: 0.161

EpiControl AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.50
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.054
Sift	Benign	0.24	T
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.093
MPC		0.20
ClinPred		0.058	T
GERP RS		0.17
Varity_R		0.069
gMVP		0.13
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7269320; hg19: chr20-3846397; COSMIC: COSV63926941;