NM_014647.4:c.5005G>A

Variant names:

• chr16-15596917-C-T
• rs776029755
• NM_014647.4:c.5005G>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.5005G>A​(p.Glu1669Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000871 in 1,606,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: MARF1 NM_014647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• 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=0.10625628).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

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.5005G>A	p.Glu1669Lys	missense	Exon 27 of 27	NP_055462.2	Q9Y4F3-1
	MARF1	NM_001184998.2		c.5005G>A	p.Glu1669Lys	missense	Exon 27 of 27	NP_001171927.1	Q9Y4F3-5
	MARF1	NM_001184999.2		c.4996G>A	p.Glu1666Lys	missense	Exon 27 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.5005G>A	p.Glu1669Lys	missense	Exon 27 of 27	ENSP00000379654.3	Q9Y4F3-1
	MARF1	ENST00000551742.5	TSL:1	c.5005G>A	p.Glu1669Lys	missense	Exon 27 of 27	ENSP00000450309.1	Q9Y4F3-5
	MARF1	ENST00000548025.5	TSL:1	c.4996G>A	p.Glu1666Lys	missense	Exon 27 of 27	ENSP00000449376.1	Q9Y4F3-4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152126 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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 246922 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000357

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000688 AC: 10 AN: 1454436 Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 9 AN XY: 722302

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 44234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.00 AC: 0 AN: 85542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00000903 AC: 10 AN: 1106998

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000580 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.089
Eigen_PC	Benign	0.094
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.031
Sift	Uncertain	0.011	D
Sift4G	Benign	0.35	T
Vest4		0.23
MVP		0.15
MPC		0.63
ClinPred		0.37	T
GERP RS		5.5
Varity_R		0.13
gMVP		0.28
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776029755; hg19: chr16-15690774;