Genetic Variant NM_014647.4:c.4830G>C (chr16-15599008-C-G) – 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_014647.4(MARF1):c.4830G>C(p.Glu1610Asp) 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 1,456,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1610Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MARF1
NM_014647.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.335

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: 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=0.106025994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARF1	NM_014647.4 link	c.4830G>C	p.Glu1610Asp	missense_variant	Exon 26 of 27	ENST00000396368.8	NP_055462.2	Q9Y4F3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARF1	ENST00000396368.8 link	c.4830G>C	p.Glu1610Asp	missense_variant	Exon 26 of 27	1	NM_014647.4	ENSP00000379654.3		Q9Y4F3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33288

American (AMR)

AF:

0.00

AC:

AN:

43796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25656

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

85774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109862

Other (OTH)

AF:

0.0000166

AC:

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4830G>C (p.E1610D) alteration is located in exon 26 (coding exon 25) of the KIAA0430 gene. This alteration results from a G to C substitution at nucleotide position 4830, causing the glutamic acid (E) at amino acid position 1610 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;.;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;.;.;N

PhyloP100

-0.34

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Vest4

0.29

MVP

0.14

MPC

0.46

ClinPred

0.45

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.40

Mutation Taster

=82/18

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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NM_014647.4:c.4830G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over