chr8-143567423-G-T

Variant names:

• chr8-143567423-G-T
• rs746796492
• NM_001100878.2:c.1976C>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.1976C>A​(p.Ala659Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000854 in 1,170,336 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. A659T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• 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=0.052210808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.1976C>A	p.Ala659Glu	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.1976C>A	p.Ala659Glu	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 8.54e-7 AC: 1 AN: 1170336 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 562540

⚠️ 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: 23904

American (AMR) AF: 0.00 AC: 0 AN: 11088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15928

East Asian (EAS) AF: 0.00 AC: 0 AN: 27556

South Asian (SAS) AF: 0.00 AC: 0 AN: 44510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3176

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 967242

Other (OTH) AF: 0.00 AC: 0 AN: 47506

⚠️ 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.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.13
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.079
Sift	Benign	1.0	T
Sift4G	Uncertain	0.027	D
Polyphen		0.010	B
Vest4		0.18
MutPred		0.29		Loss of glycosylation at S664 (P = 0.0825);
MVP		0.030
MPC		0.052
ClinPred		0.14	T
GERP RS		2.6
Varity_R		0.043
gMVP		0.16
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs746796492; hg19: chr8-144649593;