8-143567393-G-A

Variant names:

• chr8-143567393-G-A
• rs947413611
• NM_001100878.2:c.2006C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001100878.2(MROH6):​c.2006C>T​(p.Ala669Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,252,670 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: 𝑓 0.00018 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.380
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037865639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2006C>T	p.Ala669Val	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.2006C>T	p.Ala669Val	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 151836 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.000427 AC: 1 AN: 2344 AF XY: 0.000747

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0455

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000155 AC: 171 AN: 1100726 Hom.: 0 Cov.: 45 AF XY: 0.000163 AC XY: 85 AN XY: 522674

African (AFR) AF: 0.000348 AC: 8 AN: 22986

American (AMR) AF: 0.00 AC: 0 AN: 8612

Ashkenazi Jewish (ASJ) AF: 0.00554 AC: 81 AN: 14614

East Asian (EAS) AF: 0.0000377 AC: 1 AN: 26520

South Asian (SAS) AF: 0.000298 AC: 8 AN: 26836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22870

Middle Eastern (MID) AF: 0.00169 AC: 5 AN: 2964

European-Non Finnish (NFE) AF: 0.0000526 AC: 49 AN: 930820

Other (OTH) AF: 0.000427 AC: 19 AN: 44504

GnomAD4 genome AF: 0.000184 AC: 28 AN: 151944 Hom.: 0 Cov.: 36 AF XY: 0.000162 AC XY: 12 AN XY: 74280

African (AFR) AF: 0.0000241 AC: 1 AN: 41498

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67886

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000174

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2006C>T (p.A669V) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a C to T substitution at nucleotide position 2006, causing the alanine (A) at amino acid position 669 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.071	N
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.38
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.021
Sift	Benign	0.085	T
Sift4G	Benign	0.32	T
Polyphen		0.0050	B
Vest4		0.041
MutPred		0.22		Gain of catalytic residue at A669 (P = 0.1247);
MVP		0.014
MPC		0.018
ClinPred		0.041	T
GERP RS		0.89
Varity_R		0.030
gMVP		0.10
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs947413611; hg19: chr8-144649563;