5-10372506-T-C

Variant names:

• chr5-10372506-T-C
• rs2607292
• NM_005885.4:c.20-5292T>C

Variant summary

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

The NM_005885.4(MARCHF6):​c.20-5292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 151,520 control chromosomes in the GnomAD database, including 47,948 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 0.78 (47948 hom., cov: 31)
• Consequence: MARCHF6 NM_005885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 19 publications found

Genes affected

MARCHF6 (HGNC:30550): (membrane associated ring-CH-type finger 6) This gene encodes a member of a family of membrane-associated E3 ubiquitin ligases containing RING-CH-type zinc finger motifs. Ubiquitination of type II deiodinase by the encoded protein is an important regulatory step in thyroid hormone signalling. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

MARCHF6 Gene-Disease associations (from GenCC):

• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF6	NM_005885.4	c.20-5292T>C		intron_variant	Intron 1 of 25	ENST00000274140.10	NP_005876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF6	ENST00000274140.10	c.20-5292T>C		intron_variant	Intron 1 of 25	1	NM_005885.4	ENSP00000274140.4

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118518 AN: 151406 Hom.: 47957 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.782 AC: 118531 AN: 151520 Hom.: 47948 Cov.: 31 AF XY: 0.775 AC XY: 57358 AN XY: 74058

African (AFR) AF: 0.655 AC: 26817 AN: 40916

American (AMR) AF: 0.688 AC: 10499 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3203 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5182

South Asian (SAS) AF: 0.683 AC: 3291 AN: 4816

European-Finnish (FIN) AF: 0.889 AC: 9379 AN: 10552

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60950 AN: 68012

Other (OTH) AF: 0.798 AC: 1686 AN: 2112

Alfa AF: 0.850 Hom.: 116531

Bravo AF: 0.755

Asia WGS AF: 0.476 AC: 1650 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		0.13
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: rs2607292; hg19: chr5-10372618;