1-170971859-C-T

Variant names:

• chr1-170971859-C-T
• NM_001163629.2:c.592C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.879

Genes affected

MROH9 (HGNC:26287): (maestro heat like repeat family member 9)

ENSG00000231424 (HGNC:40240):

ACMG classification

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
MROH9	NM_001163629.2	c.592C>T	p.Leu198Phe	missense_variant	Exon 8 of 22	ENST00000367759.9	NP_001157101.1
MROH9	NM_025063.4	c.592C>T	p.Leu198Phe	missense_variant	Exon 8 of 15		NP_079339.2
MROH9	XM_011510005.3	c.592C>T	p.Leu198Phe	missense_variant	Exon 8 of 21		XP_011508307.1
MROH9	XM_011510006.3	c.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
MROH9	ENST00000367759.9	c.592C>T	p.Leu198Phe	missense_variant	Exon 8 of 22	5	NM_001163629.2	ENSP00000356733.4

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

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;