rs766367988

Variant names:

• chr5-16179185-C-A
• NM_001102562.3:c.391G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-16179185-C-A
• chr5-16179185-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102562.3(MARCHF11):​c.391G>T​(p.Glu131*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000835 in 1,197,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: MARCHF11 NM_001102562.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF11	NM_001102562.3	c.391G>T	p.Glu131*	stop_gained	Exon 1 of 4	ENST00000332432.9	NP_001096032.1
MARCHF11	XM_047417230.1	c.391G>T	p.Glu131*	stop_gained	Exon 1 of 3		XP_047273186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF11	ENST00000332432.9	c.391G>T	p.Glu131*	stop_gained	Exon 1 of 4	5	NM_001102562.3	ENSP00000333181.7
MARCHF11	ENST00000505509.1	n.119-1304G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.35e-7 AC: 1 AN: 1197278 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 583388

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.0018	N
Vest4		0.055
GERP RS		2.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-16179294;