chr8-143567381-C-G

Variant names:

• chr8-143567381-C-G
• rs1454898107
• NM_001100878.2:c.2018G>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.2018G>C​(p.Arg673Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,086,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R673H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• 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=0.10361752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2018G>C	p.Arg673Pro	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.2018G>C	p.Arg673Pro	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 9.21e-7 AC: 1 AN: 1086118 Hom.: 0 Cov.: 45 AF XY: 0.00000195 AC XY: 1 AN XY: 514006

African (AFR) AF: 0.00 AC: 0 AN: 22812

American (AMR) AF: 0.00 AC: 0 AN: 8304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14292

East Asian (EAS) AF: 0.00 AC: 0 AN: 26360

South Asian (SAS) AF: 0.00 AC: 0 AN: 22546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2926

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 923238

Other (OTH) AF: 0.00 AC: 0 AN: 43838

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.0
DANN	Benign	0.67
DEOGEN2	Benign	0.010	T;.;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.24	.;.;.;T;.
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L;.;.;.;.
PhyloP100		-0.86
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N;D;D;D;D
REVEL	Benign	0.045
Sift	Benign	0.063	T;T;T;T;.
Sift4G	Uncertain	0.036	D;T;T;T;.
Polyphen		0.61	P;.;.;.;.
Vest4		0.33
MutPred		0.34		Loss of methylation at R673 (P = 0.0029);.;.;.;.;
MVP		0.030
MPC		0.053
ClinPred		0.24	T
GERP RS		-1.8
Varity_R		0.26
gMVP		0.37
Mutation Taster		=96/4	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: rs1454898107; hg19: chr8-144649551;