10-45517829-A-T

Variant names:

• chr10-45517829-A-T
• rs970548
• NM_001282866.2:c.102+15281T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282866.2(MARCHF8):​c.102+15281T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MARCHF8 NM_001282866.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 64 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282866.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF8	NM_001282866.2	MANE Select	c.102+15281T>A		intron	N/A	NP_001269795.1	Q5T0T0-2
	MARCHF8	NM_001401645.1		c.102+15281T>A		intron	N/A	NP_001388574.1	Q5T0T0-2
	MARCHF8	NM_001401646.1		c.102+15281T>A		intron	N/A	NP_001388575.1	Q5T0T0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF8	ENST00000453424.7	TSL:1 MANE Select	c.102+15281T>A		intron	N/A	ENSP00000411848.2	Q5T0T0-2
	MARCHF8	ENST00000319836.7	TSL:1	c.102+15281T>A		intron	N/A	ENSP00000317087.3	Q5T0T0-1
	MARCHF8	ENST00000395769.6	TSL:1	c.102+15281T>A		intron	N/A	ENSP00000379116.2	Q5T0T0-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14846

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.5
DANN	Benign	0.77
PhyloP100		-0.53

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: rs970548; hg19: chr10-46013277;