chr8-143567412-C-G

Variant names:

• chr8-143567412-C-G
• rs891016985
• ENST00000533679.5:c.-21G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100878.2(MROH6):​c.1987G>C​(p.Val663Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000863 in 1,158,900 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V663M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16377121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.1987G>C	p.Val663Leu	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.1987G>C	p.Val663Leu	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 8.63e-7 AC: 1 AN: 1158900 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 556310

African (AFR) AF: 0.00 AC: 0 AN: 23738

American (AMR) AF: 0.00 AC: 0 AN: 10724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15688

East Asian (EAS) AF: 0.00 AC: 0 AN: 27338

South Asian (SAS) AF: 0.00 AC: 0 AN: 42220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 961658

Other (OTH) AF: 0.0000213 AC: 1 AN: 46996

GnomAD4 genome Cov.: 36

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.61	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.044
Sift	Benign	0.069	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.25
MutPred		0.25		Loss of catalytic residue at V663 (P = 0.0199);
MVP		0.040
MPC		0.046
ClinPred		0.37	T
GERP RS		3.4
Varity_R		0.090
gMVP		0.10
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs891016985; hg19: chr8-144649582;