NM_001102562.3:c.530C>T

Variant names:

• chr5-16179046-G-A
• rs1450776373
• NM_001102562.3:c.530C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001102562.3(MARCHF11):​c.530C>T​(p.Ala177Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000527 in 1,328,540 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: 0.0000053 (0 hom.)
• Consequence: MARCHF11 NM_001102562.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3205735).

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.530C>T	p.Ala177Val	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.530C>T	p.Ala177Val	missense	Exon 1 of 4	ENSP00000333181.7	A6NNE9-1
	MARCHF11	ENST00000505509.1	TSL:3	n.119-1165C>T		intron	N/A
	MARCHF11-DT	ENST00000757949.1		n.208+3202G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000527 AC: 7 AN: 1328540 Hom.: 0 Cov.: 34 AF XY: 0.00000305 AC XY: 2 AN XY: 654726

African (AFR) AF: 0.00 AC: 0 AN: 26742

American (AMR) AF: 0.00 AC: 0 AN: 28458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22966

East Asian (EAS) AF: 0.000135 AC: 4 AN: 29624

South Asian (SAS) AF: 0.00 AC: 0 AN: 74552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.00000285 AC: 3 AN: 1054246

Other (OTH) AF: 0.00 AC: 0 AN: 55212

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.48
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.011	D
Polyphen		0.91	P
Vest4		0.24
MutPred		0.56		Loss of sheet (P = 0.0817)
MVP		0.78
MPC		0.45
ClinPred		0.92	D
GERP RS		3.5
Varity_R		0.16
gMVP		0.43
Mutation Taster		=68/32	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

dbSNP: rs1450776373; hg19: chr5-16179155;