chr16-15596809-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014647.4(MARF1):​c.5113G>A​(p.Glu1705Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,613,914 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 (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

MARF1
NM_014647.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Publications

1 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]
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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08619702).
BS2
High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MARF1NM_014647.4 linkc.5113G>A p.Glu1705Lys missense_variant Exon 27 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.5113G>A p.Glu1705Lys missense_variant Exon 27 of 27 1 NM_014647.4 ENSP00000379654.3 Q9Y4F3-1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000206
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000882
AC:
22
AN:
249494
AF XY:
0.000103
show subpopulations
Gnomad AFR exome
AF:
0.0000646
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:
0.000168
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000251
AC:
367
AN:
1461796
Hom.:
0
Cov.:
31
AF XY:
0.000235
AC XY:
171
AN XY:
727202
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000308
AC:
343
AN:
1111946
Other (OTH)
AF:
0.000348
AC:
21
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
20
40
60
80
100
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
20
40
60
80
100
<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
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74304
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41408
American (AMR)
AF:
0.00
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000206
AC:
14
AN:
68020
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000328
Hom.:
0
Bravo
AF:
0.000106
ESP6500AA
AF:
0.000251
AC:
1
ESP6500EA
AF:
0.000238
AC:
2
ExAC
AF:
0.0000579
AC:
7
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 02, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.5113G>A (p.E1705K) alteration is located in exon 27 (coding exon 26) of the KIAA0430 gene. This alteration results from a G to A substitution at nucleotide position 5113, causing the glutamic acid (E) at amino acid position 1705 to be replaced by a lysine (K). 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
0.079
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.013
T;.;.;.
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.086
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;.;.;L
PhyloP100
2.5
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.39
N;N;N;N
REVEL
Benign
0.064
Sift
Uncertain
0.010
D;D;D;D
Sift4G
Benign
0.097
T;T;T;T
Vest4
0.16
MVP
0.12
MPC
0.76
ClinPred
0.047
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.084
gMVP
0.17
Mutation Taster
=91/9
polymorphism

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

Other links and lift over

dbSNP: rs201906029; hg19: chr16-15690666; API