chr1-54653259-T-A

Position:

• chr1-54653259-T-A

Variant summary

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

The NM_001039464.4(MROH7):​c.333T>A​(p.Asp111Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MROH7 NM_001039464.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.821

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=0.056580484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH7	NM_001039464.4	c.333T>A	p.Asp111Glu	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.333T>A	p.Asp111Glu	missense_variant	3/24	2	NM_001039464.4	ENSP00000396622.2
MROH7-TTC4	ENST00000414150.6	n.333T>A		non_coding_transcript_exon_variant	3/33	2		ENSP00000410192.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

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

Sep 26, 2024

The c.333T>A (p.D111E) alteration is located in exon 3 (coding exon 1) of the MROH7 gene. This alteration results from a T to A substitution at nucleotide position 333, causing the aspartic acid (D) at amino acid position 111 to be replaced by a glutamic acid (E). 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	0.096
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.86
DEOGEN2	Benign	0.0034	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	.;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.14	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.091	B;B;.
Vest4		0.032
MutPred		0.10		Loss of glycosylation at S109 (P = 0.2337);Loss of glycosylation at S109 (P = 0.2337);Loss of glycosylation at S109 (P = 0.2337);
MVP		0.014
MPC		0.070
ClinPred		0.032	T
GERP RS		1.2
Varity_R		0.040
gMVP		0.055

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: chr1-55118932;