rs116835087

Variant names:

• chr17-62736109-C-T
• rs116835087
• NM_152598.4:c.1759G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_152598.4(MARCHF10):​c.1759G>A​(p.Gly587Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,614,126 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: MARCHF10 NM_152598.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.62
• Publications: 7 publications found

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]

MARCHF10-AS1 (HGNC:58173):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002909094).
• BP6: Variant 17-62736109-C-T is Benign according to our data. Variant chr17-62736109-C-T is described in ClinVar as Benign. ClinVar VariationId is 3043695.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1809/152246) while in subpopulation AFR AF = 0.0422 (1753/41534). AF 95% confidence interval is 0.0406. There are 47 homozygotes in GnomAd4. There are 874 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152598.4. 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
	MARCHF10	NM_152598.4	MANE Select	c.1759G>A	p.Gly587Ser	missense	Exon 6 of 11	NP_689811.2	A0A140VKA1
	MARCHF10	NM_001288779.2		c.1873G>A	p.Gly625Ser	missense	Exon 7 of 12	NP_001275708.1	J3KTN9
	MARCHF10	NM_001100875.3		c.1759G>A	p.Gly587Ser	missense	Exon 6 of 11	NP_001094345.1	Q8NA82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF10	ENST00000311269.10	TSL:2 MANE Select	c.1759G>A	p.Gly587Ser	missense	Exon 6 of 11	ENSP00000311496.5	Q8NA82
	MARCHF10	ENST00000583600.5	TSL:1	c.1873G>A	p.Gly625Ser	missense	Exon 7 of 12	ENSP00000463080.1	J3KTN9
	MARCHF10	ENST00000456609.6	TSL:1	c.1759G>A	p.Gly587Ser	missense	Exon 6 of 11	ENSP00000416177.2	Q8NA82

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1808 AN: 152128 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

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: 0.000103

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00305 AC: 766 AN: 251244 AF XY: 0.00226

Gnomad AFR exome AF: 0.0433

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00120 AC: 1755 AN: 1461880 Hom.: 37 Cov.: 32 AF XY: 0.00102 AC XY: 741 AN XY: 727242

African (AFR) AF: 0.0432 AC: 1446 AN: 33480

American (AMR) AF: 0.00157 AC: 70 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000773 AC: 86 AN: 1112006

Other (OTH) AF: 0.00240 AC: 145 AN: 60396

GnomAD4 genome AF: 0.0119 AC: 1809 AN: 152246 Hom.: 47 Cov.: 32 AF XY: 0.0117 AC XY: 874 AN XY: 74438

African (AFR) AF: 0.0422 AC: 1753 AN: 41534

American (AMR) AF: 0.00223 AC: 34 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00449 Hom.: 13

Bravo AF: 0.0130

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0393 AC: 173

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00371 AC: 451

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MARCHF10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.58
DEOGEN2	Benign	0.0067	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.035
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.067
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.62	T
Polyphen		0.97	D
Vest4		0.073
MVP		0.35
MPC		0.22
ClinPred		0.058	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs116835087; hg19: chr17-60813470;