dbSNP rs200467003: MARF1:p.Val1533Leu (chr16-15602020-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014647.4(MARF1):c.4597G>T(p.Val1533Leu) 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 1,461,754 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. V1533M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MARF1
NM_014647.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.652

Publications

0 publications found

Variant links:

Genes affected

MARF1 (HGNC:29562): (meiosis regulator and mRNA stability factor 1) This gene encodes a putative peroxisomal protein that appears to be conserved across Euteleostomi. In humans, it may be autoantigenic. [provided by RefSeq, Jul 2010]

MARF1 links:

BMERB1 (HGNC:19213): (bMERB domain containing 1) Predicted to act upstream of or within negative regulation of cell motility involved in cerebral cortex radial glia guided migration and negative regulation of microtubule depolymerization. Predicted to be located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

BMERB1 links:

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ACMG classification

Classification was made for transcript

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=0.031240106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARF1	NM_014647.4	MANE Select	c.4597G>T	p.Val1533Leu	missense	Exon 23 of 27	NP_055462.2	Q9Y4F3-1
MARF1	NM_001184998.2		c.4597G>T	p.Val1533Leu	missense	Exon 23 of 27	NP_001171927.1	Q9Y4F3-5
MARF1	NM_001184999.2		c.4588G>T	p.Val1530Leu	missense	Exon 23 of 27	NP_001171928.1	Q9Y4F3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARF1	ENST00000396368.8	TSL:1 MANE Select	c.4597G>T	p.Val1533Leu	missense	Exon 23 of 27	ENSP00000379654.3	Q9Y4F3-1
MARF1	ENST00000551742.5	TSL:1	c.4597G>T	p.Val1533Leu	missense	Exon 23 of 27	ENSP00000450309.1	Q9Y4F3-5
MARF1	ENST00000548025.5	TSL:1	c.4588G>T	p.Val1530Leu	missense	Exon 23 of 27	ENSP00000449376.1	Q9Y4F3-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111900

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.018

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0036

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.9

PhyloP100

0.65

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.64

REVEL

Benign

0.042

Sift

Benign

0.80

Sift4G

Benign

1.0

Vest4

0.14

MVP

0.26

MPC

0.50

ClinPred

0.20

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.35

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