16-15598986-C-G

Variant names:

• chr16-15598986-C-G
• rs771291028
• NM_014647.4:c.4852G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014647.4(MARF1):​c.4852G>C​(p.Asp1618His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D1618N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MARF1 NM_014647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074896395).

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.4852G>C	p.Asp1618His	missense	Exon 26 of 27	NP_055462.2	Q9Y4F3-1
	MARF1	NM_001184998.2		c.4852G>C	p.Asp1618His	missense	Exon 26 of 27	NP_001171927.1	Q9Y4F3-5
	MARF1	NM_001184999.2		c.4843G>C	p.Asp1615His	missense	Exon 26 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.4852G>C	p.Asp1618His	missense	Exon 26 of 27	ENSP00000379654.3	Q9Y4F3-1
	MARF1	ENST00000551742.5	TSL:1	c.4852G>C	p.Asp1618His	missense	Exon 26 of 27	ENSP00000450309.1	Q9Y4F3-5
	MARF1	ENST00000548025.5	TSL:1	c.4843G>C	p.Asp1615His	missense	Exon 26 of 27	ENSP00000449376.1	Q9Y4F3-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.66
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.031
Sift	Uncertain	0.014	D
Sift4G	Benign	0.17	T
Vest4		0.24
MVP		0.082
MPC		0.88
ClinPred		0.13	T
GERP RS		1.8
Varity_R		0.037
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs771291028; hg19: chr16-15692843;