Variant 5-41018350-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173489.5(MROH2B):c.2754T>A(p.Asn918Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,610,804 control chromosomes in the GnomAD database, including 101,590 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.35 ( 9338 hom., cov: 33)

Exomes 𝑓: 0.35 ( 92252 hom. )

Consequence

MROH2B
NM_173489.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Variant links:

Genes affected

MROH2B (HGNC:26857): (maestro heat like repeat family member 2B) Predicted to be involved in protein kinase A signaling. Predicted to be located in acrosomal vesicle and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MROH2B links:

MROH2B (HGNC:):

MROH2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017885566).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MROH2B	NM_173489.5 linkuse as main transcript	c.2754T>A	p.Asn918Lys	missense_variant	27/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2 linkuse as main transcript	c.2754T>A	p.Asn918Lys	missense_variant	27/43		XP_011512254.1
MROH2B	XM_011513953.2 linkuse as main transcript	c.2568T>A	p.Asn856Lys	missense_variant	26/41		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5 linkuse as main transcript	c.2754T>A	p.Asn918Lys	missense_variant	27/42	1	NM_173489.5	ENSP00000382476.4		Q7Z745-1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52802

AN:

151986

Hom.:

9333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.357

AC:

87376

AN:

245078

Hom.:

15846

AF XY:

0.361

AC XY:

47922

AN XY:

132714

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.439

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.354

AC:

516083

AN:

1458700

Hom.:

92252

Cov.:

AF XY:

0.356

AC XY:

258454

AN XY:

725358

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.446

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.347

AC:

52843

AN:

152104

Hom.:

9338

Cov.:

AF XY:

0.348

AC XY:

25848

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.357

Gnomad4 EAS

AF:

0.285

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.310

Hom.:

2438

Bravo

AF:

0.354

TwinsUK

AF:

0.352

AC:

1304

ALSPAC

AF:

0.349

AC:

1344

ESP6500AA

AF:

0.337

AC:

1262

ESP6500EA

AF:

0.335

AC:

2751

ExAC

AF:

0.352

AC:

42493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.73

DANN

Benign

0.85

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

.;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.31

N;N

REVEL

Benign

0.021

Sift

Benign

0.28

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0010

.;B

Vest4

0.099

MutPred

0.28

.;Gain of ubiquitination at N918 (P = 0.0369);

MPC

0.022

ClinPred

0.00043

GERP RS

2.2

Varity_R

0.048

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over