1-170971859-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001163629.2(MROH9):​c.592C>T​(p.Leu198Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MROH9
NM_001163629.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.879
Variant links:
Genes affected
MROH9 (HGNC:26287): (maestro heat like repeat family member 9)

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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=0.2241073).
BP6
Variant 1-170971859-C-T is Benign according to our data. Variant chr1-170971859-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2252434.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MROH9NM_001163629.2 linkc.592C>T p.Leu198Phe missense_variant Exon 8 of 22 ENST00000367759.9 NP_001157101.1 Q5TGP6-2
MROH9NM_025063.4 linkc.592C>T p.Leu198Phe missense_variant Exon 8 of 15 NP_079339.2 Q5TGP6-1
MROH9XM_011510005.3 linkc.592C>T p.Leu198Phe missense_variant Exon 8 of 21 XP_011508307.1
MROH9XM_011510006.3 linkc.592C>T p.Leu198Phe missense_variant Exon 8 of 21 XP_011508308.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MROH9ENST00000367759.9 linkc.592C>T p.Leu198Phe missense_variant Exon 8 of 22 5 NM_001163629.2 ENSP00000356733.4 Q5TGP6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 27, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
8.3
DANN
Benign
0.89
DEOGEN2
Benign
0.012
.;T
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.10
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.65
N;N
REVEL
Benign
0.13
Sift
Benign
0.12
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.25
.;B
Vest4
0.36
MutPred
0.64
Loss of catalytic residue at L198 (P = 0.1561);Loss of catalytic residue at L198 (P = 0.1561);
MVP
0.45
MPC
0.12
ClinPred
0.20
T
GERP RS
1.3
Varity_R
0.036
gMVP
0.13

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.

Other links and lift over

hg19: chr1-170941000; API