dbSNP rs148600192: MARCHF6:p.Asn202Asp (chr5-10391569-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005885.4(MARCHF6):c.604A>G(p.Asn202Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000639 in 1,611,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

MARCHF6
NM_005885.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Publications

0 publications found

Variant links:

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

MARCHF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09702888).

BS2

High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005885.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARCHF6	NM_005885.4	MANE Select	c.604A>G	p.Asn202Asp	missense	Exon 7 of 26	NP_005876.2
MARCHF6	NM_001270660.2		c.460A>G	p.Asn154Asp	missense	Exon 6 of 25	NP_001257589.1	O60337-5
MARCHF6	NM_001270661.2		c.289A>G	p.Asn97Asp	missense	Exon 4 of 23	NP_001257590.1	O60337-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARCHF6	ENST00000274140.10	TSL:1 MANE Select	c.604A>G	p.Asn202Asp	missense	Exon 7 of 26	ENSP00000274140.4	O60337-4
MARCHF6	ENST00000930189.1		c.604A>G	p.Asn202Asp	missense	Exon 7 of 27	ENSP00000600248.1
MARCHF6	ENST00000863549.1		c.604A>G	p.Asn202Asp	missense	Exon 7 of 26	ENSP00000533608.1

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151456

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000728

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000444

AC:

AN:

247564

AF XY:

0.0000447

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000633

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000637

AC:

AN:

1460444

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

726592

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33286

American (AMR)

AF:

0.0000896

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000729

AC:

AN:

1111282

Other (OTH)

AF:

0.000116

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000660

AC:

AN:

151456

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73876

show subpopulations

African (AFR)

AF:

0.0000728

AC:

AN:

41188

American (AMR)

AF:

0.000132

AC:

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Benign

-0.069

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

M_CAP

Benign

0.0048

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

PhyloP100

6.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.4

REVEL

Benign

0.086

Sift

Benign

0.23

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.58

MVP

0.14

MPC

0.78

ClinPred

0.16

GERP RS

6.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.095

gMVP

0.088

Mutation Taster

=39/61

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over