chr18-50801445-G-A

Position:

• chr18-50801445-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031939.6(MRO):​c.489C>T​(p.Ala163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,610,724 control chromosomes in the GnomAD database, including 199,309 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (16204 hom., cov: 30)
  • Exomes 𝑓: 0.50 (183105 hom.)
• Consequence: MRO NM_031939.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

Genes affected

MRO (HGNC:24121): (maestro) This gene is specifically transcribed in males before and after differentiation of testis, and the encoded protein may play an important role in a mammalian sex determination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.102 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRO	NM_031939.6	c.489C>T	p.Ala163=	synonymous_variant	6/8	ENST00000398439.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRO	ENST00000398439.8	c.489C>T	p.Ala163=	synonymous_variant	6/8	1	NM_031939.6	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68489 AN: 151696 Hom.: 16200 Cov.: 30

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.486

GnomAD3 exomes AF: 0.503 AC: 126055 AN: 250404 Hom.: 33070 AF XY: 0.505 AC XY: 68331 AN XY: 135318

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.658

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.542

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.499

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.497 AC: 725629 AN: 1458910 Hom.: 183105 Cov.: 39 AF XY: 0.499 AC XY: 362088 AN XY: 725628

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.647

Gnomad4 ASJ exome AF: 0.499

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.451 AC: 68509 AN: 151814 Hom.: 16204 Cov.: 30 AF XY: 0.456 AC XY: 33841 AN XY: 74204

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.484

Alfa AF: 0.496 Hom.: 30976

Bravo AF: 0.448

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs2276186; hg19: chr18-48327815; COSMIC: COSV56495083;