rs2849233

Variant names:

• chr18-50805183-T-C
• rs2849233
• NM_031939.6:c.400A>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T134I) has been classified as Uncertain significance.

• 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031939.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRO	NM_031939.6	MANE Select	c.400A>G	p.Thr134Ala	missense	Exon 5 of 8	NP_114145.2
	MRO	NM_001127176.3		c.442A>G	p.Thr148Ala	missense	Exon 4 of 7	NP_001120648.1
	MRO	NM_001369508.2		c.400A>G	p.Thr134Ala	missense	Exon 5 of 8	NP_001356437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRO	ENST00000398439.8	TSL:1 MANE Select	c.400A>G	p.Thr134Ala	missense	Exon 5 of 8	ENSP00000381465.2
	MRO	ENST00000256425.6	TSL:1	c.400A>G	p.Thr134Ala	missense	Exon 5 of 8	ENSP00000256425.2
	MRO	ENST00000585524.5	TSL:1	n.*212A>G		non_coding_transcript_exon	Exon 5 of 8	ENSP00000465783.1

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

GnomAD2 exomes AF: 0.366 AC: 91962 AN: 251348 AF XY: 0.370

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 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

African (AFR) AF: 0.0874 AC: 2923 AN: 33458

American (AMR) AF: 0.374 AC: 16733 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 8276 AN: 26104

East Asian (EAS) AF: 0.297 AC: 11787 AN: 39688

South Asian (SAS) AF: 0.353 AC: 30439 AN: 86140

European-Finnish (FIN) AF: 0.403 AC: 21544 AN: 53412

Middle Eastern (MID) AF: 0.312 AC: 1795 AN: 5750

European-Non Finnish (NFE) AF: 0.418 AC: 462118 AN: 1106442

Other (OTH) AF: 0.367 AC: 22109 AN: 60230

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

African (AFR) AF: 0.100 AC: 4169 AN: 41520

American (AMR) AF: 0.342 AC: 5220 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1561 AN: 5174

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4810

European-Finnish (FIN) AF: 0.401 AC: 4228 AN: 10556

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28297 AN: 67962

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.368 Hom.: 37582

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 v4.9

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
Eigen	Benign	-0.031
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.17
Sift	Benign	0.23	T
Sift4G	Uncertain	0.011	D
Polyphen		0.012	B
Vest4		0.21
MPC		0.019
ClinPred		0.028	T
GERP RS		5.7
Varity_R		0.14
gMVP		0.18
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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