chr16-15599010-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014647.4(MARF1):​c.4828G>C​(p.Glu1610Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000104 in 1,608,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MARF1
NM_014647.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22242674).
BS2
High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MARF1NM_014647.4 linkc.4828G>C p.Glu1610Gln 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
MARF1ENST00000396368.8 linkc.4828G>C p.Glu1610Gln missense_variant Exon 26 of 27 1 NM_014647.4 ENSP00000379654.3 Q9Y4F3-1

Frequencies

GnomAD3 genomes
AF:
0.0000856
AC:
13
AN:
151954
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000967
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.0000666
AC:
16
AN:
240084
Hom.:
0
AF XY:
0.0000765
AC XY:
10
AN XY:
130722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000272
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000565
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000971
Gnomad NFE exome
AF:
0.0000369
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000106
AC:
154
AN:
1456566
Hom.:
0
Cov.:
32
AF XY:
0.000104
AC XY:
75
AN XY:
724578
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000206
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000189
Gnomad4 NFE exome
AF:
0.000127
Gnomad4 OTH exome
AF:
0.0000499
GnomAD4 genome
AF:
0.0000856
AC:
13
AN:
151954
Hom.:
0
Cov.:
31
AF XY:
0.0000943
AC XY:
7
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.0000967
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000958
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000248
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4828G>C (p.E1610Q) 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 4828, causing the glutamic acid (E) at amino acid position 1610 to be replaced by a glutamine (Q). 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
0.13
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
T;.;.;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.22
T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.5
L;.;.;L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.85
N;N;N;N
REVEL
Benign
0.11
Sift
Uncertain
0.013
D;D;D;D
Sift4G
Uncertain
0.012
D;D;D;D
Vest4
0.47
MVP
0.33
MPC
0.52
ClinPred
0.15
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.085
gMVP
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761773835; hg19: chr16-15692867; API