17-62765520-T-C

Position:

• chr17-62765520-T-C

Variant summary

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

The NM_152598.4(MARCHF10):​c.211-5514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,804 control chromosomes in the GnomAD database, including 20,271 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 0.50 (20271 hom., cov: 30)
• Consequence: MARCHF10 NM_152598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF10	NM_152598.4	c.211-5514A>G		intron_variant		ENST00000311269.10	NP_689811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF10	ENST00000311269.10	c.211-5514A>G		intron_variant		2	NM_152598.4	ENSP00000311496	P2
MARCHF10	ENST00000456609.6	c.211-5514A>G		intron_variant		1		ENSP00000416177	P2
MARCHF10	ENST00000583600.5	c.211-5514A>G		intron_variant		1		ENSP00000463080	A2
MARCHF10	ENST00000544856.6	c.211-5514A>G		intron_variant		2		ENSP00000443746	A2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75359 AN: 151686 Hom.: 20263 Cov.: 30

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75379 AN: 151804 Hom.: 20271 Cov.: 30 AF XY: 0.502 AC XY: 37258 AN XY: 74188

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.508

Alfa AF: 0.567 Hom.: 48937

Bravo AF: 0.483

Asia WGS AF: 0.581 AC: 2017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.21

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: rs7226286; hg19: chr17-60842881;