chr17-7583724-G-A

Position:

• chr17-7583724-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001330073.1(MPDU1):​c.-139G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 876,800 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00073 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: MPDU1 NM_001330073.1 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.921

Genes affected

MPDU1 (HGNC:7207): (mannose-P-dolichol utilization defect 1) This gene encodes an endoplasmic reticulum membrane protein that is required for utilization of the mannose donor mannose-P-dolichol in the synthesis of lipid-linked oligosaccharides and glycosylphosphatidylinositols. Mutations in this gene result in congenital disorder of glycosylation type If. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ENSG00000233223 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000729 (111/152356) while in subpopulation NFE AF= 0.00116 (79/68034). AF 95% confidence interval is 0.000954. There are 0 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDU1	NM_001330073.1	c.-139G>A		5_prime_UTR_variant	1/6		NP_001317002.1
MPDU1	XM_006721597.3	c.-139G>A		5_prime_UTR_variant	1/6		XP_006721660.1
MPDU1	XM_006721598.4	c.-139G>A		5_prime_UTR_variant	1/6		XP_006721661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDU1	ENST00000582151	c.-139G>A		5_prime_UTR_variant	1/1			ENSP00000462500.1
ENSG00000233223	ENST00000572046.2	n.19C>T		non_coding_transcript_exon_variant	1/2	3
MPDU1	ENST00000572936.5	n.-139G>A		non_coding_transcript_exon_variant	1/7	5		ENSP00000459306.1

Frequencies

GnomAD3 genomes AF: 0.000723 AC: 110 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000930 AC: 216 AN: 232270 Hom.: 0 AF XY: 0.00100 AC XY: 128 AN XY: 127892

Gnomad AFR exome AF: 0.000426

Gnomad AMR exome AF: 0.000351

Gnomad ASJ exome AF: 0.000307

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.000895

Gnomad NFE exome AF: 0.00137

Gnomad OTH exome AF: 0.000854

GnomAD4 exome AF: 0.00103 AC: 749 AN: 724444 Hom.: 2 Cov.: 9 AF XY: 0.00106 AC XY: 411 AN XY: 388964

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.000435

Gnomad4 ASJ exome AF: 0.000463

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.000638

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.000931

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.000832 AC XY: 62 AN XY: 74498

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000787 Hom.: 0

Bravo AF: 0.000748

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.54		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.54		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs551554693; hg19: chr17-7487042;