chr1-54652960-C-G

Variant names:

• chr1-54652960-C-G
• rs1644579860
• NM_001039464.4:c.34C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039464.4(MROH7):​c.34C>G​(p.His12Asp) 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. 16/22 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: -2.27
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04853803).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039464.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	NM_001039464.4	MANE Select	c.34C>G	p.His12Asp	missense	Exon 3 of 24	NP_001034553.3	Q68CQ1-7
	MROH7	NM_001291332.2		c.-214+10992C>G		intron	N/A	NP_001278261.1
	MROH7	NR_026782.3		n.320C>G		non_coding_transcript_exon	Exon 3 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	ENST00000421030.7	TSL:2 MANE Select	c.34C>G	p.His12Asp	missense	Exon 3 of 24	ENSP00000396622.2	Q68CQ1-7
	MROH7-TTC4	ENST00000414150.6	TSL:2	n.34C>G		non_coding_transcript_exon	Exon 3 of 33	ENSP00000410192.2	A0A0A0MT08
	MROH7	ENST00000422659.5	TSL:1	n.34C>G		non_coding_transcript_exon	Exon 2 of 23	ENSP00000388181.1	Q68CQ1-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.031
DANN	Benign	0.90
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		-2.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.082
Sift	Benign	0.30	T
Sift4G	Benign	0.18	T
Polyphen		0.039	B
Vest4		0.23
MutPred		0.11		Loss of methylation at K16 (P = 0.1)
MVP		0.014
MPC		0.10
ClinPred		0.048	T
GERP RS		-3.1
Varity_R		0.039
gMVP		0.13
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1644579860; hg19: chr1-55118633;