Genetic Variant NM_001100878.2:c.2110C>T (chr8-143567289-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100878.2(MROH6):c.2110C>T(p.Arg704Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,070,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R704L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Publications

0 publications found

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18668267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2110C>T	p.Arg704Cys	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.2110C>T	p.Arg704Cys	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000747

AC:

AN:

1070310

Hom.:

Cov.:

AF XY:

0.00000989

AC XY:

AN XY:

505328

show subpopulations

African (AFR)

AF:

0.0000890

AC:

AN:

22484

American (AMR)

AF:

0.00

AC:

AN:

8098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13822

East Asian (EAS)

AF:

0.00

AC:

AN:

25810

South Asian (SAS)

AF:

0.00

AC:

AN:

19504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2848

European-Non Finnish (NFE)

AF:

0.00000328

AC:

AN:

913880

Other (OTH)

AF:

0.0000700

AC:

AN:

42858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2110C>T (p.R704C) 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 2110, causing the arginine (R) at amino acid position 704 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0068

T;.;.;.

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.059

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.68

.;.;.;T

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

L;.;.;.

PhyloP100

3.4

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.1

N;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.025

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.16

MutPred

0.16

Loss of MoRF binding (P = 0.0251);.;.;.;

MVP

0.14

MPC

0.10

ClinPred

0.86

GERP RS

5.0

Varity_R

0.16

gMVP

0.12

Mutation Taster

=98/2

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

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NM_001100878.2:c.2110C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over