rs10054110

Positions:

• chr5-41018350-A-C
• chr5-41018350-A-G
• chr5-41018350-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173489.5(MROH2B):​c.2754T>G​(p.Asn918Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MROH2B NM_173489.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091433585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2754T>G	p.Asn918Lys	missense_variant	27/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2754T>G	p.Asn918Lys	missense_variant	27/43		XP_011512254.1
MROH2B	XM_011513953.2	c.2568T>G	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	c.2754T>G	p.Asn918Lys	missense_variant	27/42	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.83
DANN	Benign	0.88
DEOGEN2	Benign	0.0030	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.020
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);
MVP		0.030
MPC		0.022
ClinPred		0.16	T
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

Other links and lift over

dbSNP: rs10054110; hg19: chr5-41018452;