rs1048691

Variant names:

• chr12-57759165-C-T
• rs1048691
• NM_138396.6:c.*268C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138396.6(MARCHF9):​c.*268C>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 0.225 in 426,384 control chromosomes in the GnomAD database, including 12,083 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 0.26 (5597 hom., cov: 33)
  • Exomes 𝑓: 0.21 (6486 hom.)
• Consequence: MARCHF9 NM_138396.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

Genes affected

MARCHF9 (HGNC:25139): (membrane associated ring-CH-type finger 9) MARCH9 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. MARCH9 induces internalization of several membrane glycoproteins and directs them to the endosomal compartment (Bartee et al., 2004 [PubMed 14722266]; Hoer et al., 2007 [PubMed 17174307]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF9	NM_138396.6	c.*268C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000266643.6	NP_612405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF9	ENST00000266643.6	c.*268C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_138396.6	ENSP00000266643.5
MARCHF9	ENST00000548358.1	c.*268C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000446758.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39617 AN: 151990 Hom.: 5585 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.206 AC: 56397 AN: 274274 Hom.: 6486 Cov.: 2 AF XY: 0.204 AC XY: 28815 AN XY: 141488

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.261 AC: 39648 AN: 152110 Hom.: 5597 Cov.: 33 AF XY: 0.258 AC XY: 19156 AN XY: 74374

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.249

Alfa AF: 0.225 Hom.: 5416

Bravo AF: 0.281

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.91

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: rs1048691; hg19: chr12-58152948;