16-15598974-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014647.4(MARF1):​c.4864G>A​(p.Val1622Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,611,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

MARF1
NM_014647.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04424408).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MARF1NM_014647.4 linkuse as main transcriptc.4864G>A p.Val1622Ile missense_variant 26/27 ENST00000396368.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MARF1ENST00000396368.8 linkuse as main transcriptc.4864G>A p.Val1622Ile missense_variant 26/271 NM_014647.4 P5Q9Y4F3-1

Frequencies

GnomAD3 genomes
AF:
0.0000594
AC:
9
AN:
151534
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000933
AC:
23
AN:
246572
Hom.:
0
AF XY:
0.000149
AC XY:
20
AN XY:
133824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000586
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000986
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000753
AC:
110
AN:
1460266
Hom.:
0
Cov.:
32
AF XY:
0.0000895
AC XY:
65
AN XY:
726380
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000711
Gnomad4 OTH exome
AF:
0.0000995
GnomAD4 genome
AF:
0.0000593
AC:
9
AN:
151650
Hom.:
0
Cov.:
31
AF XY:
0.0000675
AC XY:
5
AN XY:
74110
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000826
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000359
AC:
3
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 18, 2023The c.4864G>A (p.V1622I) alteration is located in exon 26 (coding exon 25) of the KIAA0430 gene. This alteration results from a G to A substitution at nucleotide position 4864, causing the valine (V) at amino acid position 1622 to be replaced by an isoleucine (I). 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
0.081
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.035
T;.;.;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.044
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;.;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.26
N;N;N;N
REVEL
Benign
0.045
Sift
Uncertain
0.015
D;D;D;D
Sift4G
Benign
0.10
T;T;T;T
Vest4
0.19
MVP
0.043
MPC
0.41
ClinPred
0.081
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.048
gMVP
0.24

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: rs200947981; hg19: chr16-15692831; COSMIC: COSV100705894; COSMIC: COSV100705894; API