8-143567250-G-T

Variant names:

• chr8-143567250-G-T
• rs1823661607
• NM_001100878.2:c.2149C>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.2149C>A​(p.Arg717Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000935 in 1,069,772 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. R717C) 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: -0.343
• 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=0.039521217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2149C>A	p.Arg717Ser	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.2149C>A	p.Arg717Ser	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.35e-7 AC: 1 AN: 1069772 Hom.: 0 Cov.: 30 AF XY: 0.00000198 AC XY: 1 AN XY: 505138

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22462

American (AMR) AF: 0.000124 AC: 1 AN: 8088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13840

East Asian (EAS) AF: 0.00 AC: 0 AN: 25852

South Asian (SAS) AF: 0.00 AC: 0 AN: 19448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2852

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913444

Other (OTH) AF: 0.00 AC: 0 AN: 42798

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.2
DANN	Benign	0.68
DEOGEN2	Benign	0.00032	T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.32	.;.;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;.;.;.
PhyloP100		-0.34
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.050	N;D;D;D
REVEL	Benign	0.018
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.071
MutPred		0.17		Gain of glycosylation at R717 (P = 0.0132);.;.;.;
MVP		0.014
MPC		0.019
ClinPred		0.030	T
GERP RS		-3.5
Varity_R		0.078
gMVP		0.096
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: rs1823661607; hg19: chr8-144649420;