15-74900663-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002435.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPI	NM_002435.3	MANE Select	c.*2933T>C		3_prime_UTR	Exon 8 of 8	NP_002426.1	P34949-1
	FAM219B	NM_020447.5	MANE Select	c.*1956A>G		3_prime_UTR	Exon 5 of 5	NP_065180.1	Q5XKK7-1
	MPI	NM_001330372.2		c.*2933T>C		3_prime_UTR	Exon 8 of 8	NP_001317301.1	H3BPB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPI	ENST00000352410.9	TSL:1 MANE Select	c.*2933T>C		3_prime_UTR	Exon 8 of 8	ENSP00000318318.6	P34949-1
	FAM219B	ENST00000357635.10	TSL:1 MANE Select	c.*1956A>G		3_prime_UTR	Exon 5 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.*1416A>G		3_prime_UTR	Exon 6 of 6	ENSP00000454719.1	Q5XKK7-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.393 AC: 11 AN: 28

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.104 AC: 4326 AN: 41526

American (AMR) AF: 0.437 AC: 6682 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3470

East Asian (EAS) AF: 0.180 AC: 930 AN: 5180

South Asian (SAS) AF: 0.180 AC: 871 AN: 4828

European-Finnish (FIN) AF: 0.430 AC: 4554 AN: 10588

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36644 AN: 67954

Other (OTH) AF: 0.392 AC: 827 AN: 2112

Alfa AF: 0.479 Hom.: 24420

Bravo AF: 0.371

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.55
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1127796; hg19: chr15-75193004;