Variant 18-50806705-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031939.6(MRO):c.245A>G(p.Lys82Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MRO
NM_031939.6 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRO	NM_031939.6 linkuse as main transcript	c.245A>G	p.Lys82Arg	missense_variant, splice_region_variant	4/8	ENST00000398439.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRO	ENST00000398439.8 linkuse as main transcript	c.245A>G	p.Lys82Arg	missense_variant, splice_region_variant	4/8	1	NM_031939.6	P1	Q9BYG7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.287A>G (p.K96R) alteration is located in exon 3 (coding exon 3) of the MRO gene. This alteration results from a A to G substitution at nucleotide position 287, causing the lysine (K) at amino acid position 96 to be replaced by an arginine (R). 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

0.098

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;T;T;.;.;.;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

.;T;.;T;T;T;.;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.39

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.012

MutationAssessor

Pathogenic

3.2

M;M;M;.;M;.;M;.

MutationTaster

Benign

0.60

N;N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.0

D;.;D;D;.;D;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0080

D;.;D;D;.;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

0.70

P;P;P;.;.;.;P;.

Vest4

0.38

MutPred

0.48

Loss of methylation at K82 (P = 0.0326);Loss of methylation at K82 (P = 0.0326);Loss of methylation at K82 (P = 0.0326);.;Loss of methylation at K82 (P = 0.0326);.;Loss of methylation at K82 (P = 0.0326);Loss of methylation at K82 (P = 0.0326);

MVP

0.61

MPC

0.041

ClinPred

0.95

GERP RS

5.6

Varity_R

0.26

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: -1

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over