NM_001282866.2:c.154-6647C>T

Variant names:

• chr10-45470974-G-A
• rs901683
• NM_001282866.2:c.154-6647C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001282866.2(MARCHF8):​c.154-6647C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,244 control chromosomes in the GnomAD database, including 330 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 0.062 (330 hom., cov: 32)
• Consequence: MARCHF8 NM_001282866.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 33 publications found

Genes affected

MARCHF8 (HGNC:23356): (membrane associated ring-CH-type finger 8) MARCH8 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. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

ENSG00000295473 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF8	NM_001282866.2	c.154-6647C>T		intron_variant	Intron 3 of 7	ENST00000453424.7	NP_001269795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000453424.7	c.154-6647C>T		intron_variant	Intron 3 of 7	1	NM_001282866.2	ENSP00000411848.2

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9423 AN: 152126 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0619 AC: 9426 AN: 152244 Hom.: 330 Cov.: 32 AF XY: 0.0617 AC XY: 4591 AN XY: 74436

African (AFR) AF: 0.0635 AC: 2638 AN: 41528

American (AMR) AF: 0.0503 AC: 769 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 139 AN: 3472

East Asian (EAS) AF: 0.0526 AC: 273 AN: 5188

South Asian (SAS) AF: 0.0215 AC: 104 AN: 4828

European-Finnish (FIN) AF: 0.0694 AC: 735 AN: 10590

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4578 AN: 68022

Other (OTH) AF: 0.0549 AC: 116 AN: 2114

Alfa AF: 0.0660 Hom.: 534

Bravo AF: 0.0609

Asia WGS AF: 0.0410 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.72
PhyloP100		1.4
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: rs901683; hg19: chr10-45966422;