18-50805279-C-G

Position:

• chr18-50805279-C-G

Variant summary

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

The NM_031939.6(MRO):​c.304G>C​(p.Val102Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRO NM_031939.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.293

Genes affected

MRO (HGNC:24121): (maestro) This gene is specifically transcribed in males before and after differentiation of testis, and the encoded protein may play an important role in a mammalian sex determination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.09656626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRO	NM_031939.6	c.304G>C	p.Val102Leu	missense_variant	5/8	ENST00000398439.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRO	ENST00000398439.8	c.304G>C	p.Val102Leu	missense_variant	5/8	1	NM_031939.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.346G>C (p.V116L) alteration is located in exon 4 (coding exon 4) of the MRO gene. This alteration results from a G to C substitution at nucleotide position 346, causing the valine (V) at amino acid position 116 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.97
DEOGEN2	Benign	0.016	T;T;T;.;.;.;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	.;T;.;T;T;T;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.097	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M;M;M;.;M;.;M;.
MutationTaster	Benign	0.84	N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;.;N;N;.;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.60	T;.;T;T;.;T;T;.
Sift4G	Uncertain	0.042	D;D;D;D;D;D;D;D
Polyphen		0.0040	B;B;B;.;.;.;B;.
Vest4		0.27
MutPred		0.43		Gain of loop (P = 0.3485);Gain of loop (P = 0.3485);Gain of loop (P = 0.3485);.;Gain of loop (P = 0.3485);.;Gain of loop (P = 0.3485);Gain of loop (P = 0.3485);
MVP		0.25
MPC		0.017
ClinPred		0.081	T
GERP RS		1.5
Varity_R		0.070
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-48331649;