rs201985074

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152598.4(MARCHF10):ā€‹c.1979G>Cā€‹(p.Arg660Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,184 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.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

MARCHF10
NM_152598.4 missense

Scores

13
2
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.05
Variant links:
Genes affected
MARCHF10 (HGNC:26655): (membrane associated ring-CH-type finger 10) MARCH10 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MARCHF10NM_152598.4 linkc.1979G>C p.Arg660Pro missense_variant Exon 7 of 11 ENST00000311269.10 NP_689811.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MARCHF10ENST00000311269.10 linkc.1979G>C p.Arg660Pro missense_variant Exon 7 of 11 2 NM_152598.4 ENSP00000311496.5 Q8NA82

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
32
DANN
Benign
0.97
DEOGEN2
Benign
0.27
.;T;T;.;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.92
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;.;D;D;D
M_CAP
Benign
0.062
D
MetaRNN
Pathogenic
0.91
D;D;D;D;D
MetaSVM
Uncertain
0.25
D
MutationAssessor
Pathogenic
4.3
.;H;H;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-6.8
.;D;D;.;D
REVEL
Pathogenic
0.70
Sift
Pathogenic
0.0
.;D;D;.;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
.;D;D;.;D
Vest4
0.91, 0.91, 0.91, 0.91
MutPred
0.75
.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);.;.;
MVP
0.67
MPC
0.73
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.95
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201985074; hg19: chr17-60802424; API