chr8-143567322-G-T

Variant names:

• chr8-143567322-G-T
• rs1057068230
• NM_001100878.2:c.2077C>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.2077C>A​(p.Pro693Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,219,628 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00044 (2 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.451
• Publications: 0 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=0.010900497).
• 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.2077C>A	p.Pro693Thr	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.2077C>A	p.Pro693Thr	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes AF: 0.000567 AC: 86 AN: 151720 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000954

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000398

Gnomad OTH AF: 0.00289

GnomAD2 exomes AF: 0.00256 AC: 1 AN: 390 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000435 AC: 465 AN: 1067800 Hom.: 2 Cov.: 30 AF XY: 0.000454 AC XY: 229 AN XY: 504116

African (AFR) AF: 0.000850 AC: 19 AN: 22362

American (AMR) AF: 0.00138 AC: 11 AN: 7976

Ashkenazi Jewish (ASJ) AF: 0.00315 AC: 43 AN: 13654

East Asian (EAS) AF: 0.00 AC: 0 AN: 25390

South Asian (SAS) AF: 0.000102 AC: 2 AN: 19644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20990

Middle Eastern (MID) AF: 0.00564 AC: 16 AN: 2836

European-Non Finnish (NFE) AF: 0.000346 AC: 316 AN: 912288

Other (OTH) AF: 0.00136 AC: 58 AN: 42660

GnomAD4 genome AF: 0.000566 AC: 86 AN: 151828 Hom.: 0 Cov.: 33 AF XY: 0.000674 AC XY: 50 AN XY: 74218

African (AFR) AF: 0.000434 AC: 18 AN: 41512

American (AMR) AF: 0.00105 AC: 16 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000954 AC: 1 AN: 10482

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000398 AC: 27 AN: 67802

Other (OTH) AF: 0.00286 AC: 6 AN: 2100

Alfa AF: 0.000712 Hom.: 0

Bravo AF: 0.000672

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2077C>A (p.P693T) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a C to A substitution at nucleotide position 2077, causing the proline (P) at amino acid position 693 to be replaced by a threonine (T). 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	0.085
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.2
DANN	Benign	0.72
DEOGEN2	Benign	0.0065	T;.;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.44	.;.;.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;.;.;.
PhyloP100		0.45
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N;D;D;D
REVEL	Benign	0.058
Sift	Benign	0.18	T;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.043	B;.;.;.
Vest4		0.21
MVP		0.014
MPC		0.025
ClinPred		0.021	T
GERP RS		1.4
Varity_R		0.041
gMVP		0.15
Mutation Taster		=96/4	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: rs1057068230; hg19: chr8-144649492;