15-74902149-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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]

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MPI	NM_002435.3	c.*4419C>T		3_prime_UTR_variant	8/8	ENST00000352410.9
FAM219B	NM_020447.5	c.*470G>A		3_prime_UTR_variant	5/5	ENST00000357635.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPI	ENST00000352410.9	c.*4419C>T		3_prime_UTR_variant	8/8	1	NM_002435.3	P1
FAM219B	ENST00000357635.10	c.*470G>A		3_prime_UTR_variant	5/5	1	NM_020447.5	P1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103436 AN: 152032 Hom.: 35386 Cov.: 33

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.: 0 AF XY: 0.702 AC XY: 87649 AN XY: 124826

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.881

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.680 AC: 103524 AN: 152150 Hom.: 35425 Cov.: 33 AF XY: 0.678 AC XY: 50406 AN XY: 74398

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.684

Alfa AF: 0.687 Hom.: 36495

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
Dann	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs6495127; hg19: chr15-75194490;