NM_001039464.4:c.3444G>A

Variant names:

• chr1-54702625-G-A
• rs3765018
• NM_001039464.4:c.3444G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001039464.4(MROH7):​c.3444G>A​(p.Lys1148Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,605,828 control chromosomes in the GnomAD database, including 1,545 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.029 (242 hom., cov: 32)
  • Exomes 𝑓: 0.013 (1303 hom.)
• Consequence: MROH7 NM_001039464.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 8 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.383 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

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.3444G>A	p.Lys1148Lys	splice_region synonymous	Exon 21 of 24	NP_001034553.3	Q68CQ1-7
	MROH7	NM_001291332.2		c.1998G>A	p.Lys666Lys	splice_region synonymous	Exon 19 of 22	NP_001278261.1
	MROH7	NR_026782.3		n.3746G>A		splice_region non_coding_transcript_exon	Exon 21 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	ENST00000421030.7	TSL:2 MANE Select	c.3444G>A	p.Lys1148Lys	splice_region synonymous	Exon 21 of 24	ENSP00000396622.2	Q68CQ1-7
	MROH7-TTC4	ENST00000414150.6	TSL:2	n.3444G>A		splice_region non_coding_transcript_exon	Exon 21 of 33	ENSP00000410192.2	A0A0A0MT08
	MROH7	ENST00000422659.5	TSL:1	n.*1576G>A		splice_region non_coding_transcript_exon	Exon 20 of 23	ENSP00000388181.1	Q68CQ1-8

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4425 AN: 152136 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.0314 AC: 7706 AN: 245746 AF XY: 0.0314

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.219

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.0146

GnomAD4 exome AF: 0.0133 AC: 19402 AN: 1453576 Hom.: 1303 Cov.: 31 AF XY: 0.0148 AC XY: 10672 AN XY: 723002

African (AFR) AF: 0.0679 AC: 2254 AN: 33196

American (AMR) AF: 0.0110 AC: 476 AN: 43454

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 282 AN: 25928

East Asian (EAS) AF: 0.205 AC: 8088 AN: 39506

South Asian (SAS) AF: 0.0722 AC: 6104 AN: 84594

European-Finnish (FIN) AF: 0.0000940 AC: 5 AN: 53214

Middle Eastern (MID) AF: 0.00943 AC: 54 AN: 5724

European-Non Finnish (NFE) AF: 0.000603 AC: 668 AN: 1107978

Other (OTH) AF: 0.0245 AC: 1471 AN: 59982

GnomAD4 genome AF: 0.0293 AC: 4457 AN: 152252 Hom.: 242 Cov.: 32 AF XY: 0.0312 AC XY: 2324 AN XY: 74432

African (AFR) AF: 0.0628 AC: 2611 AN: 41548

American (AMR) AF: 0.00968 AC: 148 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5164

South Asian (SAS) AF: 0.0895 AC: 431 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00101 AC: 69 AN: 68036

Other (OTH) AF: 0.0217 AC: 46 AN: 2116

Alfa AF: 0.0113 Hom.: 250

Bravo AF: 0.0309

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.66
DANN	Benign	0.46
PhyloP100		0.38
Mutation Taster		=96/4	polymorphism (auto)

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: rs3765018; hg19: chr1-55168298; COSMIC: COSV59868113; COSMIC: COSV59868113;