dbSNP rs540947267: MROH6:c.-39G>A (chr8-143567430-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001100878.2(MROH6):c.1969G>A(p.Val657Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000934 in 1,328,260 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 36)

Exomes 𝑓: 0.000091 ( 2 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.477

Publications

0 publications found

Variant links:

Genes affected

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

MROH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20388547).

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 link	c.1969G>A	p.Val657Met	missense_variant	Exon 14 of 14	ENST00000398882.8	NP_001094348.1	A6NGR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH6	ENST00000398882.8 link	c.1969G>A	p.Val657Met	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000170

AC:

AN:

17650

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000969

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00191

GnomAD4 exome

AF:

0.0000910

AC:

107

AN:

1176236

Hom.:

Cov.:

AF XY:

0.0000972

AC XY:

AN XY:

565638

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24004

American (AMR)

AF:

0.00

AC:

AN:

11280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16026

East Asian (EAS)

AF:

0.0000722

AC:

AN:

27690

South Asian (SAS)

AF:

0.00119

AC:

AN:

45494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30960

Middle Eastern (MID)

AF:

0.000942

AC:

AN:

3186

European-Non Finnish (NFE)

AF:

0.0000381

AC:

AN:

969872

Other (OTH)

AF:

0.000230

AC:

AN:

47724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41516

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000584

AC:

AN:

5138

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67912

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1969G>A (p.V657M) 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 1969, causing the valine (V) at amino acid position 657 to be replaced by a methionine (M). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.069

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.17

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.9

PhyloP100

-0.48

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

REVEL

Benign

0.17

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.35

MutPred

0.40

Gain of glycosylation at P655 (P = 0.0977);

MVP

0.085

MPC

0.14

ClinPred

0.16

GERP RS

4.8

Varity_R

0.11

gMVP

0.27

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs540947267

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over