chr8-143567336-G-C

Variant names:

• chr8-143567336-G-C
• rs1354177421
• NM_001100878.2:c.2063C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100878.2(MROH6):​c.2063C>G​(p.Pro688Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000574 in 1,218,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P688L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.705
• Publications: 0 publications found

Genes affected

MROH6 (HGNC:27814): (maestro heat like repeat family member 6)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05561936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2063C>G	p.Pro688Arg	missense_variant	Exon 14 of 14	ENST00000398882.8	NP_001094348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH6	ENST00000398882.8	c.2063C>G	p.Pro688Arg	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151370 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000468 AC: 5 AN: 1067482 Hom.: 0 Cov.: 30 AF XY: 0.00000595 AC XY: 3 AN XY: 504012

African (AFR) AF: 0.00 AC: 0 AN: 22364

American (AMR) AF: 0.00 AC: 0 AN: 7960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13648

East Asian (EAS) AF: 0.00 AC: 0 AN: 25408

South Asian (SAS) AF: 0.00 AC: 0 AN: 19782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2834

European-Non Finnish (NFE) AF: 0.00000439 AC: 4 AN: 911812

Other (OTH) AF: 0.0000234 AC: 1 AN: 42654

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151370 Hom.: 0 Cov.: 33 AF XY: 0.0000271 AC XY: 2 AN XY: 73924

African (AFR) AF: 0.00 AC: 0 AN: 41336

American (AMR) AF: 0.0000658 AC: 1 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67634

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2063C>G (p.P688R) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a C to G substitution at nucleotide position 2063, causing the proline (P) at amino acid position 688 to be replaced by an arginine (R). 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	0.056
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.9
DANN	Benign	0.53
DEOGEN2	Benign	0.00028	T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.36	.;.;.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L;.;.;.
PhyloP100		0.70
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.020	N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.61	T;T;T;T
Sift4G	Uncertain	0.037	D;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.13
MutPred		0.24		Gain of MoRF binding (P = 0.0064);.;.;.;
MVP		0.014
MPC		0.018
ClinPred		0.017	T
GERP RS		-4.9
Varity_R		0.029
gMVP		0.063
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1354177421; hg19: chr8-144649506;