Genetic Variant ENST00000399577.9:c.*534G>A (chr16-4686833-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000399577.9(MGRN1):c.*534G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 985,992 control chromosomes in the GnomAD database, including 165,326 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 0.53 ( 21923 hom., cov: 33)

Exomes 𝑓: 0.59 ( 143403 hom. )

Consequence

MGRN1
ENST00000399577.9 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526

Publications

15 publications found

Variant links:

Genes affected

MGRN1 (HGNC:20254): (mahogunin ring finger 1) Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of signal transduction; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MGRN1 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399577.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGRN1	NM_015246.4	MANE Select	c.1619-1963G>A	intron	N/A	NP_056061.1	O60291-2
MGRN1	NM_001142290.3		c.*534G>A	3_prime_UTR	Exon 17 of 17	NP_001135762.1	O60291-1
MGRN1	NM_001142291.3		c.*534G>A	3_prime_UTR	Exon 16 of 16	NP_001135763.2	O60291-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGRN1	ENST00000399577.9	TSL:1	c.*534G>A	3_prime_UTR	Exon 17 of 17	ENSP00000382487.4	O60291-1
MGRN1	ENST00000415496.5	TSL:1	c.*534G>A	3_prime_UTR	Exon 16 of 16	ENSP00000393311.2	O60291-4
MGRN1	ENST00000262370.12	TSL:1 MANE Select	c.1619-1963G>A	intron	N/A	ENSP00000262370.6	O60291-2

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80502

AN:

151946

Hom.:

21885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.579

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.511

GnomAD4 exome

AF:

0.585

AC:

487850

AN:

833928

Hom.:

143403

Cov.:

AF XY:

0.585

AC XY:

225331

AN XY:

385148

show subpopulations

African (AFR)

AF:

0.436

AC:

6905

AN:

15828

American (AMR)

AF:

0.485

AC:

481

AN:

992

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

2723

AN:

5192

East Asian (EAS)

AF:

0.629

AC:

2298

AN:

3652

South Asian (SAS)

AF:

0.435

AC:

7176

AN:

16482

European-Finnish (FIN)

AF:

0.563

AC:

179

AN:

318

Middle Eastern (MID)

AF:

0.554

AC:

899

AN:

1624

European-Non Finnish (NFE)

AF:

0.592

AC:

451668

AN:

762472

Other (OTH)

AF:

0.567

AC:

15521

AN:

27368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13838

27676

41514

55352

69190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16836

33672

50508

67344

84180

<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:

0.530

AC:

80586

AN:

152064

Hom.:

21923

Cov.:

AF XY:

0.527

AC XY:

39174

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.437

AC:

18111

AN:

41462

American (AMR)

AF:

0.485

AC:

7404

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1785

AN:

3472

East Asian (EAS)

AF:

0.657

AC:

3389

AN:

5162

South Asian (SAS)

AF:

0.444

AC:

2140

AN:

4816

European-Finnish (FIN)

AF:

0.579

AC:

6140

AN:

10606

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.587

AC:

39920

AN:

67954

Other (OTH)

AF:

0.505

AC:

1066

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1932

3864

5796

7728

9660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.480

Hom.:

2678

Bravo

AF:

0.522

Asia WGS

AF:

0.505

AC:

1757

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.45

(source)

DANN

Benign

0.85

PhyloP100

-0.53

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over