chr5-40998133-C-T

Position:

• chr5-40998133-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_173489.5(MROH2B):​c.4677G>A​(p.Pro1559Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,600,780 control chromosomes in the GnomAD database, including 124,677 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 0.37 (10793 hom., cov: 32)
  • Exomes 𝑓: 0.39 (113884 hom.)
• Consequence: MROH2B NM_173489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.636 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4677G>A	p.Pro1559Pro	synonymous_variant	42/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513953.2	c.4491G>A	p.Pro1497Pro	synonymous_variant	41/41		XP_011512255.1
MROH2B	XM_011513952.2	c.*42G>A		3_prime_UTR_variant	43/43		XP_011512254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4677G>A	p.Pro1559Pro	synonymous_variant	42/42	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56518 AN: 151924 Hom.: 10788 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.375 AC: 92438 AN: 246424 Hom.: 17969 AF XY: 0.372 AC XY: 49709 AN XY: 133680

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.297

Gnomad SAS exome AF: 0.311

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.392 AC: 567747 AN: 1448736 Hom.: 113884 Cov.: 33 AF XY: 0.390 AC XY: 280873 AN XY: 721066

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.372 AC: 56545 AN: 152044 Hom.: 10793 Cov.: 32 AF XY: 0.373 AC XY: 27712 AN XY: 74320

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.362

Alfa AF: 0.380 Hom.: 15070

Bravo AF: 0.362

Asia WGS AF: 0.271 AC: 942 AN: 3478

EpiCase AF: 0.401

EpiControl AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.39
DANN	Benign	0.36

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: rs722575; hg19: chr5-40998235; COSMIC: COSV68181071;