chr16-15600490-C-A

Variant names:

• chr16-15600490-C-A
• rs768760857
• NM_014647.4:c.4751G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014647.4(MARF1):​c.4751G>T​(p.Arg1584Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1584H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MARF1 NM_014647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 3 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04127896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARF1	NM_014647.4	MANE Select	c.4751G>T	p.Arg1584Leu	missense	Exon 25 of 27	NP_055462.2	Q9Y4F3-1
	MARF1	NM_001184998.2		c.4751G>T	p.Arg1584Leu	missense	Exon 25 of 27	NP_001171927.1	Q9Y4F3-5
	MARF1	NM_001184999.2		c.4742G>T	p.Arg1581Leu	missense	Exon 25 of 27	NP_001171928.1	Q9Y4F3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARF1	ENST00000396368.8	TSL:1 MANE Select	c.4751G>T	p.Arg1584Leu	missense	Exon 25 of 27	ENSP00000379654.3	Q9Y4F3-1
	MARF1	ENST00000551742.5	TSL:1	c.4751G>T	p.Arg1584Leu	missense	Exon 25 of 27	ENSP00000450309.1	Q9Y4F3-5
	MARF1	ENST00000548025.5	TSL:1	c.4742G>T	p.Arg1581Leu	missense	Exon 25 of 27	ENSP00000449376.1	Q9Y4F3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.1
DANN	Benign	0.74
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.12
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.083
Sift	Benign	0.29	T
Sift4G	Benign	0.12	T
Vest4		0.15
MVP		0.093
MPC		0.64
ClinPred		0.032	T
GERP RS		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.27

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: rs768760857; hg19: chr16-15694347;