NM_138396.6:c.*268C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF9	NM_138396.6	MANE Select	c.*268C>T		3_prime_UTR	Exon 4 of 4	NP_612405.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF9	ENST00000266643.6	TSL:1 MANE Select	c.*268C>T		3_prime_UTR	Exon 4 of 4	ENSP00000266643.5
	MARCHF9	ENST00000548358.1	TSL:1	c.*268C>T		3_prime_UTR	Exon 2 of 2	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

African (AFR) AF: 0.341 AC: 3121 AN: 9160

American (AMR) AF: 0.352 AC: 3626 AN: 10288

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 1436 AN: 9756

East Asian (EAS) AF: 0.143 AC: 3147 AN: 22044

South Asian (SAS) AF: 0.146 AC: 2456 AN: 16816

European-Finnish (FIN) AF: 0.228 AC: 4262 AN: 18700

Middle Eastern (MID) AF: 0.206 AC: 270 AN: 1308

European-Non Finnish (NFE) AF: 0.203 AC: 34434 AN: 169286

Other (OTH) AF: 0.215 AC: 3645 AN: 16916

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

African (AFR) AF: 0.345 AC: 14294 AN: 41470

American (AMR) AF: 0.355 AC: 5434 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3468

East Asian (EAS) AF: 0.163 AC: 843 AN: 5160

South Asian (SAS) AF: 0.159 AC: 767 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2382 AN: 10606

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14559 AN: 67982

Other (OTH) AF: 0.249 AC: 525 AN: 2110

Alfa AF: 0.232 Hom.: 13163

Bravo AF: 0.281

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		0.61
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: rs1048691; hg19: chr12-58152948;