8-144190855-A-G

Position:

• chr8-144190855-A-G

Variant summary

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

The NM_032450.3(MROH1):​c.634A>G​(p.Arg212Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MROH1 NM_032450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

Genes affected

MROH1 (HGNC:26958): (maestro heat like repeat family member 1)

MROH1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH1	NM_032450.3	c.634A>G	p.Arg212Gly	missense_variant	8/44	ENST00000326134.10	NP_115826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH1	ENST00000326134.10	c.634A>G	p.Arg212Gly	missense_variant	8/44	5	NM_032450.3	ENSP00000321737.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Mar 25, 2024

The c.634A>G (p.R212G) alteration is located in exon 8 (coding exon 6) of the MROH1 gene. This alteration results from a A to G substitution at nucleotide position 634, causing the arginine (R) at amino acid position 212 to be replaced by a glycine (G). 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	0.32
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	.;.;T;T
Eigen	Benign	0.064
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D;D;.;D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.5	M;.;M;M
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.9	D;D;D;D
REVEL	Uncertain	0.47
Sift	Benign	0.078	T;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.027	B;D;D;D
Vest4		0.90
MutPred		0.30		Loss of solvent accessibility (P = 0.1235);Loss of solvent accessibility (P = 0.1235);Loss of solvent accessibility (P = 0.1235);Loss of solvent accessibility (P = 0.1235);
MVP		0.53
MPC		0.30
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.56

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: chr8-145245758;