chr8-143567336-G-T

Variant names:

• chr8-143567336-G-T
• rs1354177421
• NM_001100878.2:c.2063C>A

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.2063C>A​(p.Pro688Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,067,478 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. P688R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• 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=0.0620856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2063C>A	p.Pro688Gln	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.2063C>A	p.Pro688Gln	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1067478 Hom.: 0 Cov.: 30 AF XY: 0.00000198 AC XY: 1 AN XY: 504010

African (AFR) AF: 0.00 AC: 0 AN: 22364

American (AMR) AF: 0.00 AC: 0 AN: 7960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13648

East Asian (EAS) AF: 0.00 AC: 0 AN: 25408

South Asian (SAS) AF: 0.00 AC: 0 AN: 19780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2834

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 911810

Other (OTH) AF: 0.00 AC: 0 AN: 42654

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.6
DANN	Benign	0.74
DEOGEN2	Benign	0.0012	T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.35	.;.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L;.;.;.
PhyloP100		0.70
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.10	N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.62	T;T;T;T
Sift4G	Uncertain	0.037	D;T;T;T
Polyphen		0.017	B;.;.;.
Vest4		0.23
MutPred		0.19		Loss of catalytic residue at P688 (P = 0.012);.;.;.;
MVP		0.014
MPC		0.022
ClinPred		0.020	T
GERP RS		-4.9
Varity_R		0.028
gMVP		0.073
Mutation Taster		=100/0	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: rs1354177421; hg19: chr8-144649506;