NM_001100878.2:c.2117G>T

Variant names:

• chr8-143567282-C-A
• NM_001100878.2:c.2117G>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.2117G>T​(p.Ser706Ile) 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 1,070,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• 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=0.18737552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH6	NM_001100878.2	MANE Select	c.2117G>T	p.Ser706Ile	missense	Exon 14 of 14	NP_001094348.1	A6NGR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH6	ENST00000398882.8	TSL:5 MANE Select	c.2117G>T	p.Ser706Ile	missense	Exon 14 of 14	ENSP00000381857.3	A6NGR9
	MROH6	ENST00000533679.5	TSL:1	c.110G>T	p.Ser37Ile	missense	Exon 5 of 5	ENSP00000434244.1	E9PJR4
	MROH6	ENST00000533210.5	TSL:1	n.1222G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.34e-7 AC: 1 AN: 1070926 Hom.: 0 Cov.: 30 AF XY: 0.00000198 AC XY: 1 AN XY: 505618

African (AFR) AF: 0.00 AC: 0 AN: 22504

American (AMR) AF: 0.000123 AC: 1 AN: 8116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13870

East Asian (EAS) AF: 0.00 AC: 0 AN: 25886

South Asian (SAS) AF: 0.00 AC: 0 AN: 19510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21014

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914282

Other (OTH) AF: 0.00 AC: 0 AN: 42890

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.017
Eigen_PC	Benign	-0.092
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.17		Loss of phosphorylation at S706 (P = 0.0242)
MVP		0.15
MPC		0.062
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.34
Mutation Taster		=94/6	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

hg19: chr8-144649452;