rs2251393

Positions:

• chr17-62701571-G-A
• chr17-62701571-G-C
• chr17-62701571-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152598.4(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_152598.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF10	NM_152598.4	c.*132C>T		3_prime_UTR_variant	11/11	ENST00000311269.10	NP_689811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF10	ENST00000311269.10	c.*132C>T		3_prime_UTR_variant	11/11	2	NM_152598.4	ENSP00000311496	P2

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

GnomAD3 exomes AF: 0.846 AC: 191793 AN: 226626 Hom.: 81532 AF XY: 0.851 AC XY: 104738 AN XY: 123042

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 SAS exome AF: 0.852

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

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.838

Gnomad4 EAS exome AF: 0.895

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.860

Gnomad4 OTH exome AF: 0.850

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

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.802

Alfa AF: 0.848 Hom.: 76518

Bravo AF: 0.798

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.4
DANN	Benign	0.86

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: rs2251393; hg19: chr17-60778932; COSMIC: COSV60884919; COSMIC: COSV60884919;