rs3802548

Positions:

• chr10-45457297-T-A
• chr10-45457297-T-C

Variant summary

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

The NM_001282866.2(MARCHF8):​c.*942A>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 0.232 in 152,150 control chromosomes in the GnomAD database, including 4,304 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 0.23 (4303 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: MARCHF8 NM_001282866.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF8	NM_001282866.2	c.*942A>T		3_prime_UTR_variant	8/8	ENST00000453424.7	NP_001269795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000453424	c.*942A>T		3_prime_UTR_variant	8/8	1	NM_001282866.2	ENSP00000411848.2
MARCHF8	ENST00000319836.7	c.*942A>T		3_prime_UTR_variant	7/7	1		ENSP00000317087.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35262 AN: 152024 Hom.: 4299 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0598

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.232 AC: 35278 AN: 152144 Hom.: 4303 Cov.: 33 AF XY: 0.235 AC XY: 17516 AN XY: 74390

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0599

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.244

Alfa AF: 0.232 Hom.: 526

Bravo AF: 0.228

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.8
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: rs3802548; hg19: chr10-45952745;