8-143567340-C-A

Variant names:

• chr8-143567340-C-A
• rs1262344813
• NM_001100878.2:c.2059G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100878.2(MROH6):​c.2059G>T​(p.Ala687Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,068,566 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. A687T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05895087).

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.2059G>T	p.Ala687Ser	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.2059G>T	p.Ala687Ser	missense	Exon 14 of 14	ENSP00000381857.3	A6NGR9
	MROH6	ENST00000533679.5	TSL:1	c.52G>T	p.Ala18Ser	missense	Exon 5 of 5	ENSP00000434244.1	E9PJR4
	MROH6	ENST00000533210.5	TSL:1	n.1164G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1068566 Hom.: 0 Cov.: 30 AF XY: 0.00000198 AC XY: 1 AN XY: 504604

African (AFR) AF: 0.00 AC: 0 AN: 22396

American (AMR) AF: 0.00 AC: 0 AN: 7968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13668

East Asian (EAS) AF: 0.00 AC: 0 AN: 25454

South Asian (SAS) AF: 0.00 AC: 0 AN: 19970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2844

European-Non Finnish (NFE) AF: 0.00000219 AC: 2 AN: 912496

Other (OTH) AF: 0.00 AC: 0 AN: 42726

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.026
DANN	Benign	0.73
DEOGEN2	Benign	0.00024	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.010
Sift	Benign	0.64	T
Sift4G	Benign	0.55	T
Polyphen		0.24	B
Vest4		0.078
MutPred		0.14		Gain of phosphorylation at A687 (P = 0.0035)
MVP		0.014
MPC		0.017
ClinPred		0.055	T
GERP RS		1.2
Varity_R		0.034
gMVP		0.056
Mutation Taster		=99/1	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: rs1262344813; hg19: chr8-144649510;