17-62725011-G-A

Variant names:

• chr17-62725011-G-A
• rs111291268
• NM_152598.4:c.2031C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_152598.4(MARCHF10):​c.2031C>T​(p.Cys677Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,610,320 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0028 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (22 hom.)
• Consequence: MARCHF10 NM_152598.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.793

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]

ENSG00000265702 (HGNC:58173):

LOC105371855 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-62725011-G-A is Benign according to our data. Variant chr17-62725011-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038174.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.793 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF10	NM_152598.4	c.2031C>T	p.Cys677Cys	synonymous_variant	Exon 7 of 11	ENST00000311269.10	NP_689811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF10	ENST00000311269.10	c.2031C>T	p.Cys677Cys	synonymous_variant	Exon 7 of 11	2	NM_152598.4	ENSP00000311496.5

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 422 AN: 152198 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00475

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00236 AC: 582 AN: 246700 Hom.: 3 AF XY: 0.00226 AC XY: 302 AN XY: 133468

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00435

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.00487 AC: 7105 AN: 1458004 Hom.: 22 Cov.: 31 AF XY: 0.00467 AC XY: 3389 AN XY: 725246

Gnomad4 AFR exome AF: 0.000480

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.0000767

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.00611

Gnomad4 OTH exome AF: 0.00315

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152316 Hom.: 4 Cov.: 32 AF XY: 0.00228 AC XY: 170 AN XY: 74496

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00475

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.00299

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MARCHF10-related disorder Benign:1

Mar 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.1
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs111291268; hg19: chr17-60802372;