Genetic Variant NM_031939.6:c.489C>T (chr18-50801445-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_031939.6(MRO):c.489C>T(p.Ala163Ala) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.102

Publications

14 publications found

Variant links:

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]

MRO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRO	NM_031939.6 link	c.489C>T	p.Ala163Ala	synonymous_variant	Exon 6 of 8	ENST00000398439.8	NP_114145.2	Q9BYG7-1A0A024R2B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRO	ENST00000398439.8 link	c.489C>T	p.Ala163Ala	synonymous_variant	Exon 6 of 8	1	NM_031939.6	ENSP00000381465.2		Q9BYG7-1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68489

AN:

151696

Hom.:

16200

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.503

AC:

126055

AN:

250404

AF XY:

0.505

show subpopulations

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 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.:

AF XY:

0.499

AC XY:

362088

AN XY:

725628

show subpopulations

African (AFR)

AF:

0.295

AC:

9865

AN:

33422

American (AMR)

AF:

0.647

AC:

28830

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

13004

AN:

26038

East Asian (EAS)

AF:

0.354

AC:

14035

AN:

39652

South Asian (SAS)

AF:

0.546

AC:

46814

AN:

85798

European-Finnish (FIN)

AF:

0.509

AC:

27121

AN:

53316

Middle Eastern (MID)

AF:

0.512

AC:

2947

AN:

5754

European-Non Finnish (NFE)

AF:

0.499

AC:

553687

AN:

1110164

Other (OTH)

AF:

0.487

AC:

29326

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

17735

35471

53206

70942

88677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16186

32372

48558

64744

80930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.451

AC:

68509

AN:

151814

Hom.:

16204

Cov.:

AF XY:

0.456

AC XY:

33841

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.308

AC:

12730

AN:

41360

American (AMR)

AF:

0.557

AC:

8495

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1780

AN:

3472

East Asian (EAS)

AF:

0.366

AC:

1887

AN:

5158

South Asian (SAS)

AF:

0.549

AC:

2649

AN:

4826

European-Finnish (FIN)

AF:

0.514

AC:

5406

AN:

10518

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.500

AC:

33935

AN:

67928

Other (OTH)

AF:

0.484

AC:

1021

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1834

3667

5501

7334

9168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.492

Hom.:

37265

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

(source)

DANN

Benign

0.57

PhyloP100

0.10

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over