1-54653140-G-A

Position:

• chr1-54653140-G-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.214G>A​(p.Ala72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MROH7 NM_001039464.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.145

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=0.04019028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH7	NM_001039464.4	c.214G>A	p.Ala72Thr	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.214G>A	p.Ala72Thr	missense_variant	3/24	2	NM_001039464.4	ENSP00000396622.2
MROH7-TTC4	ENST00000414150.6	n.214G>A		non_coding_transcript_exon_variant	3/33	2		ENSP00000410192.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 46 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Oct 08, 2024

The c.214G>A (p.A72T) alteration is located in exon 3 (coding exon 1) of the MROH7 gene. This alteration results from a G to A substitution at nucleotide position 214, causing the alanine (A) at amino acid position 72 to be replaced by a threonine (T). 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	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.81
DEOGEN2	Benign	0.0032	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.14	.;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.16	N;N;N
REVEL	Benign	0.0050
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.037
MutPred		0.22		Gain of phosphorylation at A72 (P = 0.035);Gain of phosphorylation at A72 (P = 0.035);Gain of phosphorylation at A72 (P = 0.035);
MVP		0.014
MPC		0.069
ClinPred		0.050	T
GERP RS		1.4
Varity_R		0.024
gMVP		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-55118813;