17-62701571-G-A

Variant names:

• chr17-62701571-G-A
• rs2251393
• NM_152598.4:c.*132C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288779.2(MARCHF10):​c.*132C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,571,044 control chromosomes in the GnomAD database, including 570,887 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50770 hom., cov: 32)
  • Exomes 𝑓: 0.86 (520117 hom.)
• Consequence: MARCHF10 NM_001288779.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288779.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF10	NM_152598.4	MANE Select	c.*132C>T		3_prime_UTR	Exon 11 of 11	NP_689811.2
	MARCHF10	NM_001288779.2		c.*132C>T		3_prime_UTR	Exon 12 of 12	NP_001275708.1
	MARCHF10	NM_001100875.3		c.*132C>T		3_prime_UTR	Exon 11 of 11	NP_001094345.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF10	ENST00000311269.10	TSL:2 MANE Select	c.*132C>T		3_prime_UTR	Exon 11 of 11	ENSP00000311496.5
	MARCHF10	ENST00000583600.5	TSL:1	c.*132C>T		3_prime_UTR	Exon 12 of 12	ENSP00000463080.1
	MARCHF10	ENST00000456609.6	TSL:1	c.*132C>T		3_prime_UTR	Exon 11 of 11	ENSP00000416177.2

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123575 AN: 152050 Hom.: 50766 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.807

GnomAD2 exomes AF: 0.846 AC: 191793 AN: 226626 AF XY: 0.851

Gnomad AFR exome AF: 0.679

Gnomad AMR exome AF: 0.814

Gnomad ASJ exome AF: 0.834

Gnomad EAS exome AF: 0.908

Gnomad FIN exome AF: 0.898

Gnomad NFE exome AF: 0.864

Gnomad OTH exome AF: 0.845

GnomAD4 exome AF: 0.855 AC: 1213593 AN: 1418876 Hom.: 520117 Cov.: 29 AF XY: 0.856 AC XY: 602502 AN XY: 703896

African (AFR) AF: 0.671 AC: 21992 AN: 32764

American (AMR) AF: 0.816 AC: 35251 AN: 43178

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 20468 AN: 24430

East Asian (EAS) AF: 0.895 AC: 34934 AN: 39024

South Asian (SAS) AF: 0.857 AC: 70819 AN: 82614

European-Finnish (FIN) AF: 0.896 AC: 35428 AN: 39540

Middle Eastern (MID) AF: 0.806 AC: 4485 AN: 5562

European-Non Finnish (NFE) AF: 0.860 AC: 940294 AN: 1093036

Other (OTH) AF: 0.850 AC: 49922 AN: 58728

GnomAD4 genome AF: 0.812 AC: 123627 AN: 152168 Hom.: 50770 Cov.: 32 AF XY: 0.815 AC XY: 60640 AN XY: 74388

African (AFR) AF: 0.681 AC: 28236 AN: 41476

American (AMR) AF: 0.826 AC: 12642 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2896 AN: 3470

East Asian (EAS) AF: 0.905 AC: 4660 AN: 5150

South Asian (SAS) AF: 0.864 AC: 4159 AN: 4816

European-Finnish (FIN) AF: 0.902 AC: 9572 AN: 10616

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58802 AN: 68016

Other (OTH) AF: 0.802 AC: 1697 AN: 2116

Alfa AF: 0.834 Hom.: 131224

Bravo AF: 0.798

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.4
DANN	Benign	0.86
PhyloP100		0.32
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: rs2251393; hg19: chr17-60778932; COSMIC: COSV60884919; COSMIC: COSV60884919;