16-15596809-C-T

Variant names:

• chr16-15596809-C-T
• rs201906029
• NM_014647.4:c.5113G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• Publications: 1 publications found

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]

ACMG classification

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
MARF1	NM_014647.4	c.5113G>A	p.Glu1705Lys	missense_variant	Exon 27 of 27	ENST00000396368.8	NP_055462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARF1	ENST00000396368.8	c.5113G>A	p.Glu1705Lys	missense_variant	Exon 27 of 27	1	NM_014647.4	ENSP00000379654.3

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152118 Hom.: 0 Cov.: 33

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

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

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

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74304

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

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

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

Other links and lift over

dbSNP: rs201906029; hg19: chr16-15690666;