Genetic Variant MPI:c.*4419C>T (chr15-74902149-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002435.3(MPI):c.*4419C>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 0.695 in 398,492 control chromosomes in the GnomAD database, including 96,900 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 0.68 ( 35425 hom., cov: 33)

Exomes 𝑓: 0.70 ( 61475 hom. )

Consequence

MPI
NM_002435.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

Publications

13 publications found

Variant links:

Genes affected

MPI (HGNC:7216): (mannose phosphate isomerase) Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MPI links:

FAM219B (HGNC:24695): (family with sequence similarity 219 member B)

FAM219B links:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPI	NM_002435.3 link	c.*4419C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000352410.9	NP_002426.1	P34949-1
FAM219B	NM_020447.5 link	c.*470G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000357635.10	NP_065180.1	Q5XKK7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPI	ENST00000352410.9 link	c.*4419C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_002435.3	ENSP00000318318.6		P34949-1
FAM219B	ENST00000357635.10 link	c.*470G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_020447.5	ENSP00000350260.5		Q5XKK7-1

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

103436

AN:

152032

Hom.:

35386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.761

Gnomad AMR

AF:

0.721

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.880

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.682

GnomAD4 exome

AF:

0.704

AC:

173354

AN:

246342

Hom.:

61475

Cov.:

AF XY:

0.702

AC XY:

87649

AN XY:

124826

show subpopulations

African (AFR)

AF:

0.628

AC:

4507

AN:

7180

American (AMR)

AF:

0.754

AC:

5607

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

6051

AN:

9240

East Asian (EAS)

AF:

0.881

AC:

20164

AN:

22894

South Asian (SAS)

AF:

0.656

AC:

2003

AN:

3052

European-Finnish (FIN)

AF:

0.647

AC:

13469

AN:

20824

Middle Eastern (MID)

AF:

0.636

AC:

823

AN:

1294

European-Non Finnish (NFE)

AF:

0.691

AC:

109285

AN:

158054

Other (OTH)

AF:

0.699

AC:

11445

AN:

16370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2983

5965

8948

11930

14913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.680

AC:

103524

AN:

152150

Hom.:

35425

Cov.:

AF XY:

0.678

AC XY:

50406

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.634

AC:

26315

AN:

41484

American (AMR)

AF:

0.721

AC:

11032

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2263

AN:

3472

East Asian (EAS)

AF:

0.880

AC:

4560

AN:

5182

South Asian (SAS)

AF:

0.652

AC:

3148

AN:

4826

European-Finnish (FIN)

AF:

0.644

AC:

6821

AN:

10586

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

47037

AN:

67988

Other (OTH)

AF:

0.684

AC:

1443

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1748

3496

5243

6991

8739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.690

Hom.:

53844

Bravo

AF:

0.690

Asia WGS

AF:

0.798

AC:

2775

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.6

(source)

DANN

Benign

0.52

PhyloP100

-0.12

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