5-16179152-G-A

Variant names:

• chr5-16179152-G-A
• NM_001102562.3:c.424C>T

Variant summary

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

The NM_001102562.3(MARCHF11):​c.424C>T​(p.Arg142Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,301,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: MARCHF11 NM_001102562.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.679
• Publications: 0 publications found

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]

MARCHF11-DT (HGNC:55550): (MARCHF11 divergent transcript)

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=0.22657391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102562.3. 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
	MARCHF11	NM_001102562.3	MANE Select	c.424C>T	p.Arg142Cys	missense	Exon 1 of 4	NP_001096032.1	A6NNE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF11	ENST00000332432.9	TSL:5 MANE Select	c.424C>T	p.Arg142Cys	missense	Exon 1 of 4	ENSP00000333181.7	A6NNE9-1
	MARCHF11	ENST00000505509.1	TSL:3	n.119-1271C>T		intron	N/A
	MARCHF11-DT	ENST00000757949.1		n.208+3308G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1301110 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 640452

African (AFR) AF: 0.00 AC: 0 AN: 26262

American (AMR) AF: 0.0000422 AC: 1 AN: 23684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22344

East Asian (EAS) AF: 0.00 AC: 0 AN: 27896

South Asian (SAS) AF: 0.00 AC: 0 AN: 69676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3862

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041348

Other (OTH) AF: 0.00 AC: 0 AN: 53818

GnomAD4 genome Cov.: 30

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	0.0053
Eigen_PC	Benign	0.0010
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.68
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.093
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.12
MutPred		0.28		Loss of MoRF binding (P = 0.0162)
MVP		0.48
MPC		1.3
ClinPred		0.81	D
GERP RS		2.0
Varity_R		0.19
gMVP		0.33
Mutation Taster		=84/16	polymorphism

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

hg19: chr5-16179261;