Variant 1-54652948-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001039464.4(MROH7):c.22A>G(p.Asn8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MROH7
NM_001039464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.637

Variant links:

Genes affected

MROH7 (HGNC:24802): (maestro heat like repeat family member 7) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MROH7 links:

MROH7-TTC4 (HGNC:):

MROH7-TTC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055123508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH7	NM_001039464.4 linkuse as main transcript	c.22A>G	p.Asn8Asp	missense_variant	3/24	ENST00000421030.7	NP_001034553.3
MROH7-TTC4	NR_037639.2 linkuse as main transcript	n.465A>G		non_coding_transcript_exon_variant	3/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH7	ENST00000421030.7 linkuse as main transcript	c.22A>G	p.Asn8Asp	missense_variant	3/24	2	NM_001039464.4	ENSP00000396622	P2	Q68CQ1-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241322

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722286

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.22A>G (p.N8D) alteration is located in exon 3 (coding exon 1) of the MROH7 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the asparagine (N) at amino acid position 8 to be replaced by an aspartic acid (D). 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

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0023

.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.026

D;D;D

Sift4G

Benign

0.095

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.090

MutPred

0.072

Gain of phosphorylation at S4 (P = 0.1029);Gain of phosphorylation at S4 (P = 0.1029);Gain of phosphorylation at S4 (P = 0.1029);

MVP

0.014

MPC

0.080

ClinPred

0.065

GERP RS

2.2

Varity_R

0.073

gMVP

0.057

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over