chr1-54653092-G-C

Position:

• chr1-54653092-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039464.4(MROH7):​c.166G>C​(p.Ala56Pro) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MROH7 NM_001039464.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.181

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-TTC4 (HGNC:49180): (MROH7-TTC4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MROH7 (maestro heat-like repeat family member 7) and TTC4 (tetratricopeptide repeat domain 4) genes. Alternative splicing results in multiple transcript variants, which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to produce protein products. [provided by RefSeq, Aug 2013]

MROH7 (HGNC:):

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=0.048113883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH7	NM_001039464.4	c.166G>C	p.Ala56Pro	missense_variant	3/24	ENST00000421030.7	NP_001034553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH7	ENST00000421030.7	c.166G>C	p.Ala56Pro	missense_variant	3/24	2	NM_001039464.4	ENSP00000396622.2
MROH7-TTC4	ENST00000414150.6	n.166G>C		non_coding_transcript_exon_variant	3/33	2		ENSP00000410192.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.166G>C (p.A56P) alteration is located in exon 3 (coding exon 1) of the MROH7 gene. This alteration results from a G to C substitution at nucleotide position 166, causing the alanine (A) at amino acid position 56 to be replaced by a proline (P). 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	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.7
DANN	Benign	0.74
DEOGEN2	Benign	0.0030	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.63	.;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.055	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.26
MutPred		0.14		Gain of glycosylation at A56 (P = 0.0962);Gain of glycosylation at A56 (P = 0.0962);Gain of glycosylation at A56 (P = 0.0962);
MVP		0.014
MPC		0.091
ClinPred		0.039	T
GERP RS		-1.0
Varity_R		0.12
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: chr1-55118765;