18-50805183-T-C

Position:

• chr18-50805183-T-C

Variant summary

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

The NM_031939.6(MRO):​c.400A>G​(p.Thr134Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,608,012 control chromosomes in the GnomAD database, including 126,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.31 (8862 hom., cov: 32)
  • Exomes 𝑓: 0.40 (118043 hom.)
• Consequence: MRO NM_031939.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032892227).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRO	NM_031939.6	c.400A>G	p.Thr134Ala	missense_variant	5/8	ENST00000398439.8	NP_114145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRO	ENST00000398439.8	c.400A>G	p.Thr134Ala	missense_variant	5/8	1	NM_031939.6	ENSP00000381465.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47296 AN: 151958 Hom.: 8857 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.307

GnomAD3 exomes AF: 0.366 AC: 91962 AN: 251348 Hom.: 17883 AF XY: 0.370 AC XY: 50197 AN XY: 135844

Gnomad AFR exome AF: 0.0934

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.306

Gnomad SAS exome AF: 0.349

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.412

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.397 AC: 577724 AN: 1455936 Hom.: 118043 Cov.: 35 AF XY: 0.396 AC XY: 286802 AN XY: 724600

Gnomad4 AFR exome AF: 0.0874

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.311 AC: 47311 AN: 152076 Hom.: 8862 Cov.: 32 AF XY: 0.309 AC XY: 22993 AN XY: 74330

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.309

Alfa AF: 0.381 Hom.: 28712

Bravo AF: 0.296

TwinsUK AF: 0.434 AC: 1611

ALSPAC AF: 0.395 AC: 1522

ESP6500AA AF: 0.117 AC: 514

ESP6500EA AF: 0.401 AC: 3447

ExAC AF: 0.361 AC: 43853

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T;T;.;.;.;T;.
Eigen	Benign	-0.031
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.64	.;T;.;T;T;T;.;T
MetaRNN	Benign	0.0033	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;L;L;.;L;.;L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N;.;N;N;.;N;N;.
REVEL	Benign	0.17
Sift	Benign	0.23	T;.;T;D;.;T;T;.
Sift4G	Uncertain	0.011	D;D;D;D;D;D;D;D
Polyphen		0.012	B;B;B;.;.;.;B;.
Vest4		0.21
MPC		0.019
ClinPred		0.028	T
GERP RS		5.7
Varity_R		0.14
gMVP		0.18

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: rs2849233; hg19: chr18-48331553; COSMIC: COSV56495114;