Genetic Variant MROH7:p.Ser64Phe (chr1-54653117-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039464.4(MROH7):c.191C>T(p.Ser64Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S64C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MROH7
NM_001039464.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.225

Publications

3 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079440385).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH7	NM_001039464.4	MANE Select	c.191C>T	p.Ser64Phe	missense	Exon 3 of 24	NP_001034553.3	Q68CQ1-7
MROH7	NM_001291332.2		c.-214+11149C>T		intron	N/A	NP_001278261.1
MROH7	NR_026782.3		n.477C>T		non_coding_transcript_exon	Exon 3 of 24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH7	ENST00000421030.7	TSL:2 MANE Select	c.191C>T	p.Ser64Phe	missense	Exon 3 of 24	ENSP00000396622.2	Q68CQ1-7
MROH7-TTC4	ENST00000414150.6	TSL:2	n.191C>T		non_coding_transcript_exon	Exon 3 of 33	ENSP00000410192.2	A0A0A0MT08
MROH7	ENST00000422659.5	TSL:1	n.191C>T		non_coding_transcript_exon	Exon 2 of 23	ENSP00000388181.1	Q68CQ1-8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249270

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.72

M_CAP

Benign

0.0092

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

PhyloP100

-0.23

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

REVEL

Benign

0.030

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.14

Vest4

0.23

MutPred

0.31

Gain of catalytic residue at S64 (P = 0.0315)

MVP

0.030

MPC

0.11

ClinPred

0.12

GERP RS

2.7

Varity_R

0.079

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over