15-74900663-T-C

Variant names:

• chr15-74900663-T-C
• rs1127796
• NM_002435.3:c.*2933T>C

Variant summary

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

The NM_002435.3(MPI):​c.*2933T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,164 control chromosomes in the GnomAD database, including 13,537 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 0.37 (13532 hom., cov: 32)
  • Exomes 𝑓: 0.44 (5 hom.)
• Consequence: MPI NM_002435.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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 (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPI	NM_002435.3	c.*2933T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000352410.9	NP_002426.1
FAM219B	NM_020447.5	c.*1956A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000357635.10	NP_065180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPI	ENST00000352410.9	c.*2933T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_002435.3	ENSP00000318318.6
FAM219B	ENST00000357635	c.*1956A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_020447.5	ENSP00000350260.5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56948 AN: 152014 Hom.: 13532 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.438 AC: 14 AN: 32 Hom.: 5 Cov.: 0 AF XY: 0.462 AC XY: 12 AN XY: 26

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.374 AC: 56954 AN: 152132 Hom.: 13532 Cov.: 32 AF XY: 0.365 AC XY: 27154 AN XY: 74382

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.392

Alfa AF: 0.491 Hom.: 19418

Bravo AF: 0.371

Asia WGS AF: 0.178 AC: 622 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	4.9
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1127796; hg19: chr15-75193004;