Genetic Variant MROH6:p.Leu505Phe (chr8-143568683-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001100878.2(MROH6):c.1513C>T(p.Leu505Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000733 in 1,364,954 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L505P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Variant links:

Genes affected

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

MROH6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27203512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.1513C>T	p.Leu505Phe	missense_variant	Exon 10 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.1513C>T	p.Leu505Phe	missense_variant	Exon 10 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.33e-7

AC:

AN:

1364954

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30346

American (AMR)

AF:

0.00

AC:

AN:

31804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24086

East Asian (EAS)

AF:

0.00

AC:

AN:

35202

South Asian (SAS)

AF:

0.00

AC:

AN:

77164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069550

Other (OTH)

AF:

0.00

AC:

AN:

56816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1513C>T (p.L505F) alteration is located in exon 10 (coding exon 10) of the MROH6 gene. This alteration results from a C to T substitution at nucleotide position 1513, causing the leucine (L) at amino acid position 505 to be replaced by a phenylalanine (F). 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

0.25

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.00079

Eigen

Benign

-0.018

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.60

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

5.4

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

2.6

REVEL

Benign

0.23

Sift

Benign

1.0

Sift4G

Pathogenic

0.0

Polyphen

0.46

Vest4

0.54

MutPred

0.47

Loss of disorder (P = 0.0665);

MVP

0.16

MPC

2.1

ClinPred

0.36

GERP RS

4.0

PromoterAI

0.018

Neutral

(source)

Varity_R

0.073

gMVP

0.24

Mutation Taster

=290/10

polymorphism

(source)

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over