10-92352399-G-C

Variant names:

• chr10-92352399-G-C
• rs1057848
• NM_017824.5:c.*1192G>C

Variant summary

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

The NM_017824.5(MARCHF5):​c.*1192G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,080 control chromosomes in the GnomAD database, including 10,769 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 0.34 (10769 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: MARCHF5 NM_017824.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975
• Publications: 6 publications found

Genes affected

MARCHF5 (HGNC:26025): (membrane associated ring-CH-type finger 5) MARCH5 is a ubiquitin ligase of the mitochondrial outer membrane that plays a role in the control of mitochondrial morphology by regulating mitofusin-2 (MFN2; MIM 608507) and DRP1 (DNM1L; MIM 603850) (Nakamura et al., 2006 [PubMed 16936636]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF5	NM_017824.5	c.*1192G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000358935.3	NP_060294.1
MARCHF5	XM_047425382.1	c.*1192G>C		3_prime_UTR_variant	Exon 6 of 6		XP_047281338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF5	ENST00000358935.3	c.*1192G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_017824.5	ENSP00000351813.2

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51051 AN: 151962 Hom.: 10779 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.409

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.336 AC: 51028 AN: 152080 Hom.: 10769 Cov.: 33 AF XY: 0.328 AC XY: 24369 AN XY: 74316

African (AFR) AF: 0.109 AC: 4534 AN: 41500

American (AMR) AF: 0.357 AC: 5454 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5184

South Asian (SAS) AF: 0.245 AC: 1184 AN: 4824

European-Finnish (FIN) AF: 0.363 AC: 3824 AN: 10530

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32151 AN: 67982

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.286 Hom.: 876

Bravo AF: 0.328

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.4
DANN	Benign	0.83
PhyloP100		0.97
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: rs1057848; hg19: chr10-94112156;