rs11539762

Variant names:

• chr11-69296043-G-A
• rs11539762
• NM_001293291.2:c.593G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001293291.2(MYEOV):​c.593G>A​(p.Arg198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,614,078 control chromosomes in the GnomAD database, including 13,260 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1073 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12187 hom.)
• Consequence: MYEOV NM_001293291.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

MYEOV (HGNC:7563): (myeloma overexpressed)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055698156).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYEOV	NM_001293291.2	c.593G>A	p.Arg198Gln	missense_variant	Exon 3 of 3	ENST00000441339.3	NP_001280220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYEOV	ENST00000441339.3	c.593G>A	p.Arg198Gln	missense_variant	Exon 3 of 3	2	NM_001293291.2	ENSP00000412482.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17097 AN: 152098 Hom.: 1075 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.130 AC: 32669 AN: 251362 Hom.: 2617 AF XY: 0.138 AC XY: 18704 AN XY: 135856

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0759

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.196

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.0749

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.121 AC: 176999 AN: 1461862 Hom.: 12187 Cov.: 34 AF XY: 0.125 AC XY: 91152 AN XY: 727228

Gnomad4 AFR exome AF: 0.0970

Gnomad4 AMR exome AF: 0.0772

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.112 AC: 17106 AN: 152216 Hom.: 1073 Cov.: 33 AF XY: 0.114 AC XY: 8503 AN XY: 74394

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0960

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.0669

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.117

Alfa AF: 0.115 Hom.: 1348

Bravo AF: 0.109

TwinsUK AF: 0.111 AC: 412

ALSPAC AF: 0.125 AC: 482

ESP6500AA AF: 0.0984 AC: 433

ESP6500EA AF: 0.108 AC: 925

ExAC AF: 0.134 AC: 16288

Asia WGS AF: 0.222 AC: 771 AN: 3478

EpiCase AF: 0.113

EpiControl AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.95
DANN	Benign	0.97
DEOGEN2	Benign	0.0024	T;T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.52	.;T;T
MetaRNN	Benign	0.0056	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.093
Polyphen		0.98	D;D;.
Vest4		0.019
MPC		0.33
ClinPred		0.012	T
GERP RS		1.4
Varity_R		0.22
gMVP		0.068

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11539762; hg19: chr11-69063510; COSMIC: COSV58293488; COSMIC: COSV58293488;