rs704040

Positions:

• chr5-40998094-T-A
• chr5-40998094-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173489.5(MROH2B):​c.4716A>T​(p.Gln1572His) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MROH2B NM_173489.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33082238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4716A>T	p.Gln1572His	missense_variant	42/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513953.2	c.4530A>T	p.Gln1510His	missense_variant	41/41		XP_011512255.1
MROH2B	XM_011513952.2	c.*81A>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.4716A>T	p.Gln1572His	missense_variant	42/42	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459440 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 726084

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	0.089
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.0	.;M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.12
Sift	Benign	0.18	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.83	.;P
Vest4		0.48
MutPred		0.39		.;Loss of disorder (P = 0.0414);
MVP		0.16
MPC		0.098
ClinPred		0.88	D
GERP RS		3.8
Varity_R		0.061
gMVP		0.21

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: rs704040; hg19: chr5-40998196;