rs13158763

Positions:

• chr5-16093521-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102562.3(MARCHF11):​c.694-2440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,714 control chromosomes in the GnomAD database, including 7,907 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7907 hom., cov: 31)
• Consequence: MARCHF11 NM_001102562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

Genes affected

MARCHF11 (HGNC:33609): (membrane associated ring-CH-type finger 11) MARCH11 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). These enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their intracellular transport. March11 appears to have a role in ubiquitin-mediated protein sorting in the trans-Golgi network (TGN)-multivesicular body (MVB) transport pathway (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF11	NM_001102562.3	c.694-2440C>T		intron_variant		ENST00000332432.9	NP_001096032.1
MARCHF11	XM_047417230.1	c.694-25728C>T		intron_variant			XP_047273186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF11	ENST00000332432.9	c.694-2440C>T		intron_variant		5	NM_001102562.3	ENSP00000333181.7
MARCHF11	ENST00000507111.1	c.103-25728C>T		intron_variant		3		ENSP00000424425.1
MARCHF11	ENST00000505509.1	n.275-2440C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45311 AN: 151596 Hom.: 7896 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45348 AN: 151714 Hom.: 7907 Cov.: 31 AF XY: 0.312 AC XY: 23153 AN XY: 74094

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.301

Alfa AF: 0.316 Hom.: 1471

Bravo AF: 0.289

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs13158763; hg19: chr5-16093630;