rs761773835

Variant names:

• chr16-15599010-C-G
• rs761773835
• NM_014647.4:c.4828G>C

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.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. 12/21 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. E1610D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MARF1 NM_014647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79
• Publications: 0 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=0.22242674).
• BS2: High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARF1	NM_014647.4	c.4828G>C	p.Glu1610Gln	missense_variant	Exon 26 of 27	ENST00000396368.8	NP_055462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARF1	ENST00000396368.8	c.4828G>C	p.Glu1610Gln	missense_variant	Exon 26 of 27	1	NM_014647.4	ENSP00000379654.3

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151954 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.0000666 AC: 16 AN: 240084 AF XY: 0.0000765

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33236

American (AMR) AF: 0.000206 AC: 9 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25660

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85752

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1109794

Other (OTH) AF: 0.0000499 AC: 3 AN: 60116

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151954 Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7 AN XY: 74208

African (AFR) AF: 0.0000967 AC: 4 AN: 41362

American (AMR) AF: 0.000262 AC: 4 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67980

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

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

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
PhyloP100		6.8
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
Mutation Taster		=69/31	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: rs761773835; hg19: chr16-15692867;