NM_001100878.2:c.2129G>T

Variant names:

• chr8-143567270-C-A
• rs757730419
• NM_001100878.2:c.2129G>T

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.2129G>T​(p.Arg710Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,070,320 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. R710C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 1 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=0.07964265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2129G>T	p.Arg710Leu	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.2129G>T	p.Arg710Leu	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.34e-7 AC: 1 AN: 1070320 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 505334

African (AFR) AF: 0.00 AC: 0 AN: 22470

American (AMR) AF: 0.00 AC: 0 AN: 8100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13844

East Asian (EAS) AF: 0.00 AC: 0 AN: 25874

South Asian (SAS) AF: 0.00 AC: 0 AN: 19478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2854

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 913842

Other (OTH) AF: 0.00 AC: 0 AN: 42854

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.0034	T;.;.;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.54	.;.;.;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L;.;.;.
PhyloP100		0.15
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.96	N;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.23	T;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.0020	B;.;.;.
Vest4		0.17
MutPred		0.20		Loss of methylation at R710 (P = 0.0115);.;.;.;
MVP		0.048
MPC		0.018
ClinPred		0.10	T
GERP RS		2.0
Varity_R		0.056
gMVP		0.12
Mutation Taster		=97/3	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: rs757730419; hg19: chr8-144649440;