dbSNP rs3802548: MARCHF8:c.*942A>T (chr10-45457297-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282866.2(MARCHF8):c.*942A>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 0.232 in 152,150 control chromosomes in the GnomAD database, including 4,304 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 0.23 ( 4303 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

MARCHF8
NM_001282866.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.229

Publications

6 publications found

Variant links:

Genes affected

MARCHF8 (HGNC:23356): (membrane associated ring-CH-type finger 8) MARCH8 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. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

MARCHF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF8	NM_001282866.2 link	c.*942A>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000453424.7	NP_001269795.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MARCHF8	ENST00000453424.7 link	c.*942A>T	3_prime_UTR_variant	Exon 8 of 8	1	NM_001282866.2	ENSP00000411848.2	Q5T0T0-2
MARCHF8	ENST00000319836.7 link	c.*942A>T	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000317087.3	Q5T0T0-1
MARCHF8	ENST00000395769.6 link	c.*942A>T	downstream_gene_variant		1		ENSP00000379116.2	Q5T0T0-1
MARCHF8	ENST00000476962.1 link	n.*214A>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35262

AN:

152024

Hom.:

4299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.0598

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.232

AC:

35278

AN:

152144

Hom.:

4303

Cov.:

AF XY:

0.235

AC XY:

17516

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.195

AC:

8112

AN:

41496

American (AMR)

AF:

0.296

AC:

4521

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

604

AN:

3466

East Asian (EAS)

AF:

0.0599

AC:

311

AN:

5192

South Asian (SAS)

AF:

0.253

AC:

1220

AN:

4820

European-Finnish (FIN)

AF:

0.282

AC:

2979

AN:

10574

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16673

AN:

67988

Other (OTH)

AF:

0.244

AC:

515

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1401

2802

4202

5603

7004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.232

Hom.:

526

Bravo

AF:

0.228

Asia WGS

AF:

0.204

AC:

711

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.8

(source)

DANN

Benign

0.86

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over