Genetic Variant MROH7:p.Lys1148Lys (chr1-54702625-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.383

Publications

8 publications found

Variant links:

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 links:

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-TTC4 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH7	NM_001039464.4 link	c.3444G>A	p.Lys1148Lys	splice_region_variant, synonymous_variant	Exon 21 of 24	ENST00000421030.7	NP_001034553.3	Q68CQ1-7B7Z7S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH7	ENST00000421030.7 link	c.3444G>A	p.Lys1148Lys	splice_region_variant, synonymous_variant	Exon 21 of 24	2	NM_001039464.4	ENSP00000396622.2		Q68CQ1-7
MROH7-TTC4	ENST00000414150.6 link	n.3444G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 21 of 33	2		ENSP00000410192.2		A0A0A0MT08

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4425

AN:

152136

Hom.:

232

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0148

AC XY:

10672

AN XY:

723002

show subpopulations

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:

AN:

53214

Middle Eastern (MID)

AF:

0.00943

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.000603

AC:

668

AN:

1107978

Other (OTH)

AF:

0.0245

AC:

1471

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

770

1540

2311

3081

3851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0293

AC:

4457

AN:

152252

Hom.:

242

Cov.:

AF XY:

0.0312

AC XY:

2324

AN XY:

74432

show subpopulations

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:

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:

AN:

10604

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

68036

Other (OTH)

AF:

0.0217

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

193

387

580

774

967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.66

(source)

DANN

Benign

0.46

PhyloP100

0.38

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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chr1-54702625-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over