rs12779637

Variant names:

• chr10-45585648-T-C
• rs12779637
• ENST00000319836.7:c.-79+8587A>G

Variant summary

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

The ENST00000319836.7(MARCHF8):​c.-79+8587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 152,194 control chromosomes in the GnomAD database, including 325 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 (325 hom., cov: 32)
• Consequence: MARCHF8 ENST00000319836.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF8	NM_001401645.1	c.-172+8587A>G		intron_variant	Intron 1 of 8		NP_001388574.1
MARCHF8	NM_001401646.1	c.-79+8587A>G		intron_variant	Intron 1 of 7		NP_001388575.1
MARCHF8	NM_145021.6	c.-79+8587A>G		intron_variant	Intron 1 of 6		NP_659458.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000319836.7	c.-79+8587A>G		intron_variant	Intron 1 of 6	1		ENSP00000317087.3
MARCHF8	ENST00000453980.3	c.-172+8587A>G		intron_variant	Intron 1 of 5	5		ENSP00000396678.1
MARCHF8	ENST00000602712.2	n.343+8587A>G		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9382 AN: 152076 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0617 AC: 9387 AN: 152194 Hom.: 325 Cov.: 32 AF XY: 0.0615 AC XY: 4579 AN XY: 74416

African (AFR) AF: 0.0639 AC: 2656 AN: 41540

American (AMR) AF: 0.0509 AC: 779 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3468

East Asian (EAS) AF: 0.0525 AC: 272 AN: 5180

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4826

European-Finnish (FIN) AF: 0.0685 AC: 726 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0665 AC: 4520 AN: 67972

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

Alfa AF: 0.0655 Hom.: 33

Bravo AF: 0.0606

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.54
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: rs12779637; hg19: chr10-46081096;