Variant 1-54653879-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001039464.4(MROH7):c.953A>G(p.Asn318Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)

Exomes 𝑓: 0.00077 ( 0 hom. )

Consequence

MROH7
NM_001039464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.667

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 Uncertain_significance. Variant got 0 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity MROH7_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004955739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH7	NM_001039464.4 linkuse as main transcript	c.953A>G	p.Asn318Ser	missense_variant	3/24	ENST00000421030.7	NP_001034553.3
MROH7-TTC4	NR_037639.2 linkuse as main transcript	n.1396A>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.953A>G	p.Asn318Ser	missense_variant	3/24	2	NM_001039464.4	ENSP00000396622	P2	Q68CQ1-7

Frequencies

GnomAD3 genomes

AF:

0.000574

AC:

AN:

151680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.000653

AC:

163

AN:

249568

Hom.:

AF XY:

0.000643

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000715

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000774

AC:

1131

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

554

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000798

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000573

AC:

AN:

151798

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000692

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.000778

Hom.:

Bravo

AF:

0.000646

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000594

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.000593

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

Feb 22, 2023

The c.953A>G (p.N318S) 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 953, causing the asparagine (N) at amino acid position 318 to be replaced by a serine (S). 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

0.063

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.020

DANN

Benign

0.88

DEOGEN2

Benign

0.0028

.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.14

MVP

0.014

MPC

0.060

ClinPred

0.0065

GERP RS

-6.2

Varity_R

0.027

gMVP

0.031

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