chr5-40998133-C-A

Position:

• chr5-40998133-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_173489.5(MROH2B):​c.4677G>T​(p.Pro1559Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,610,450 control chromosomes in the GnomAD database, including 1 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 0.000066 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=-0.636 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4677G>T	p.Pro1559Pro	synonymous_variant	42/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513953.2	c.4491G>T	p.Pro1497Pro	synonymous_variant	41/41		XP_011512255.1
MROH2B	XM_011513952.2	c.*42G>T		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>T	p.Pro1559Pro	synonymous_variant	42/42	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151982 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000812 AC: 20 AN: 246424 Hom.: 0 AF XY: 0.0000748 AC XY: 10 AN XY: 133680

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000501

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1458468 Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16 AN XY: 725668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000382

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: 0.0000117

Gnomad4 OTH exome AF: 0.0000664

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151982 Hom.: 1 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74212

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.27
DANN	Benign	0.39

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;