NM_001100878.2:c.2095G>C

Variant names:

• chr8-143567304-C-G
• rs537602741
• NM_001100878.2:c.2095G>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.2095G>C​(p.Asp699His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,069,324 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. D699Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743
• 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=0.13282084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2095G>C	p.Asp699His	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.2095G>C	p.Asp699His	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000374 AC: 4 AN: 1069324 Hom.: 0 Cov.: 31 AF XY: 0.00000198 AC XY: 1 AN XY: 504858

African (AFR) AF: 0.00 AC: 0 AN: 22444

American (AMR) AF: 0.00 AC: 0 AN: 8042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13772

East Asian (EAS) AF: 0.00 AC: 0 AN: 25678

South Asian (SAS) AF: 0.00 AC: 0 AN: 19538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2846

European-Non Finnish (NFE) AF: 0.00000438 AC: 4 AN: 913252

Other (OTH) AF: 0.00 AC: 0 AN: 42762

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.0072	T;.;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.51	.;.;.;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;.;.
PhyloP100		0.74
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.96	N;D;D;D
REVEL	Benign	0.070
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.032	D;T;T;T
Polyphen		0.91	P;.;.;.
Vest4		0.13
MutPred		0.12		Gain of MoRF binding (P = 0.0416);.;.;.;
MVP		0.030
MPC		0.12
ClinPred		0.48	T
GERP RS		3.2
Varity_R		0.083
gMVP		0.30
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: rs537602741; hg19: chr8-144649474;