17-62725011-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId 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

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.2031C>T	p.Cys677Cys	synonymous	Exon 7 of 11	NP_689811.2	A0A140VKA1
	MARCHF10	NM_001288779.2		c.2145C>T	p.Cys715Cys	synonymous	Exon 8 of 12	NP_001275708.1	J3KTN9
	MARCHF10	NM_001100875.3		c.2031C>T	p.Cys677Cys	synonymous	Exon 7 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.2031C>T	p.Cys677Cys	synonymous	Exon 7 of 11	ENSP00000311496.5	Q8NA82
	MARCHF10	ENST00000583600.5	TSL:1	c.2145C>T	p.Cys715Cys	synonymous	Exon 8 of 12	ENSP00000463080.1	J3KTN9
	MARCHF10	ENST00000456609.6	TSL:1	c.2031C>T	p.Cys677Cys	synonymous	Exon 7 of 11	ENSP00000416177.2	Q8NA82

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

GnomAD2 exomes AF: 0.00236 AC: 582 AN: 246700 AF XY: 0.00226

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 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

African (AFR) AF: 0.000480 AC: 16 AN: 33348

American (AMR) AF: 0.00198 AC: 87 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85256

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53392

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00611 AC: 6790 AN: 1110570

Other (OTH) AF: 0.00315 AC: 190 AN: 60276

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

African (AFR) AF: 0.00120 AC: 50 AN: 41582

American (AMR) AF: 0.00242 AC: 37 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00475 AC: 323 AN: 68022

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.00299

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.1
DANN	Benign	0.83
PhyloP100		-0.79
Mutation Taster		=95/5	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: rs111291268; hg19: chr17-60802372;