Variant 5-41005597-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173489.5(MROH2B):c.3798G>A(p.Gln1266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,612,152 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 29)

Exomes 𝑓: 0.0013 ( 6 hom. )

Consequence

MROH2B
NM_173489.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.583

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:

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

C7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-41005597-C-T is Benign according to our data. Variant chr5-41005597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 916268.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.583 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MROH2B	NM_173489.5 linkuse as main transcript	c.3798G>A	p.Gln1266=	synonymous_variant	35/42	ENST00000399564.5
MROH2B	XM_011513952.2 linkuse as main transcript	c.3798G>A	p.Gln1266=	synonymous_variant	35/43
MROH2B	XM_011513953.2 linkuse as main transcript	c.3612G>A	p.Gln1204=	synonymous_variant	34/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2B	ENST00000399564.5 linkuse as main transcript	c.3798G>A	p.Gln1266=	synonymous_variant	35/42	1	NM_173489.5	P1	Q7Z745-1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

410

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00206

AC:

508

AN:

246008

Hom.:

AF XY:

0.00181

AC XY:

241

AN XY:

133228

show subpopulations

Gnomad AFR exome

AF:

0.00526

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000269

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00451

GnomAD4 exome

AF:

0.00127

AC:

1852

AN:

1459840

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

914

AN XY:

725846

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.00355

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000327

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000730

Gnomad4 OTH exome

AF:

0.00355

GnomAD4 genome

AF:

0.00269

AC:

410

AN:

152312

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00481

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00196

Hom.:

Bravo

AF:

0.00329

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MROH2B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.30

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over