chr8-143567270-C-T

Variant names:

• chr8-143567270-C-T
• rs757730419
• NM_001100878.2:c.2129G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001100878.2(MROH6):​c.2129G>A​(p.Arg710His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,222,190 control chromosomes in the GnomAD database, including 3 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R710C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.154
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018553495).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2129G>A	p.Arg710His	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.2129G>A	p.Arg710His	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes AF: 0.000336 AC: 51 AN: 151764 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.000310

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000205 AC: 219 AN: 1070320 Hom.: 2 Cov.: 30 AF XY: 0.000226 AC XY: 114 AN XY: 505334

African (AFR) AF: 0.000223 AC: 5 AN: 22470

American (AMR) AF: 0.000741 AC: 6 AN: 8100

Ashkenazi Jewish (ASJ) AF: 0.000578 AC: 8 AN: 13844

East Asian (EAS) AF: 0.00 AC: 0 AN: 25874

South Asian (SAS) AF: 0.000616 AC: 12 AN: 19478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21004

Middle Eastern (MID) AF: 0.00561 AC: 16 AN: 2854

European-Non Finnish (NFE) AF: 0.000165 AC: 151 AN: 913842

Other (OTH) AF: 0.000490 AC: 21 AN: 42854

GnomAD4 genome AF: 0.000336 AC: 51 AN: 151870 Hom.: 1 Cov.: 32 AF XY: 0.000418 AC XY: 31 AN XY: 74226

African (AFR) AF: 0.0000241 AC: 1 AN: 41474

American (AMR) AF: 0.000916 AC: 14 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00694 AC: 2 AN: 288

European-Non Finnish (NFE) AF: 0.000310 AC: 21 AN: 67838

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000351

ExAC AF: 0.00251 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2129G>A (p.R710H) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a G to A substitution at nucleotide position 2129, causing the arginine (R) at amino acid position 710 to be replaced by a histidine (H). 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	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0054	T;.;.;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.54	.;.;.;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.019	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L;.;.;.
PhyloP100		0.15
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.0	N;D;D;D
REVEL	Benign	0.033
Sift	Benign	0.035	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.010	B;.;.;.
Vest4		0.097
MVP		0.014
MPC		0.021
ClinPred		0.44	T
GERP RS		2.0
Varity_R		0.036
gMVP		0.095
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: rs757730419; hg19: chr8-144649440;