Genetic Variant MARCHF10:c.2329-9T>G (chr17-62705590-A-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_152598.4(MARCHF10):c.2329-9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,613,622 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

MARCHF10
NM_152598.4 intron

Scores

Splicing: ADA: 0.0001096

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.52

Publications

0 publications found

Variant links:

Genes affected

MARCHF10 (HGNC:26655): (membrane associated ring-CH-type finger 10) MARCH10 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 (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]

MARCHF10 links:

MARCHF10-AS1 (HGNC:58173):

MARCHF10-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-62705590-A-C is Benign according to our data. Variant chr17-62705590-A-C is described in ClinVar as Benign. ClinVar VariationId is 3053258.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152598.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MARCHF10	NM_152598.4	MANE Select	c.2329-9T>G	intron	N/A	NP_689811.2	A0A140VKA1
MARCHF10	NM_001288779.2		c.2443-9T>G	intron	N/A	NP_001275708.1	J3KTN9
MARCHF10	NM_001100875.3		c.2329-9T>G	intron	N/A	NP_001094345.1	Q8NA82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MARCHF10	ENST00000311269.10	TSL:2 MANE Select	c.2329-9T>G	intron	N/A	ENSP00000311496.5	Q8NA82
MARCHF10	ENST00000583600.5	TSL:1	c.2443-9T>G	intron	N/A	ENSP00000463080.1	J3KTN9
MARCHF10	ENST00000456609.6	TSL:1	c.2329-9T>G	intron	N/A	ENSP00000416177.2	Q8NA82

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

372

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000658

AC:

165

AN:

250802

AF XY:

0.000450

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000255

AC:

373

AN:

1461292

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

153

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.00862

AC:

288

AN:

33418

American (AMR)

AF:

0.000337

AC:

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1111806

Other (OTH)

AF:

0.000646

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00245

AC:

373

AN:

152330

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00866

AC:

360

AN:

41574

American (AMR)

AF:

0.000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.00155

Hom.:

Bravo

AF:

0.00306

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MARCHF10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.15

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