chr17-7583724-G-A

Variant names:

• chr17-7583724-G-A
• rs551554693
• NM_001330073.1:c.-139G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BS1 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
• Publications: 0 publications found

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]

MPDU1-AS1 (HGNC:40379): (MPDU1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330073.1. 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
	MPDU1	NM_001330073.1		c.-139G>A		5_prime_UTR	Exon 1 of 6	NP_001317002.1	J3QW43
	MPDU1	NR_024603.1		n.78G>A		non_coding_transcript_exon	Exon 1 of 7
	MPDU1-AS1	NR_136401.2		n.175+194C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	ENST00000582151.1	TSL:6	c.-139G>A		5_prime_UTR	Exon 1 of 1	ENSP00000462500.1	J3KSI4
	MPDU1-AS1	ENST00000572046.3	TSL:3	n.19C>T		non_coding_transcript_exon	Exon 1 of 2
	MPDU1	ENST00000572936.5	TSL:5	n.-139G>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000459306.1	I3L1D2

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

GnomAD2 exomes AF: 0.000930 AC: 216 AN: 232270 AF XY: 0.00100

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 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

African (AFR) AF: 0.000305 AC: 6 AN: 19650

American (AMR) AF: 0.000435 AC: 19 AN: 43668

Ashkenazi Jewish (ASJ) AF: 0.000463 AC: 10 AN: 21612

East Asian (EAS) AF: 0.00 AC: 0 AN: 36518

South Asian (SAS) AF: 0.00103 AC: 73 AN: 71156

European-Finnish (FIN) AF: 0.000638 AC: 26 AN: 40758

Middle Eastern (MID) AF: 0.00200 AC: 6 AN: 2994

European-Non Finnish (NFE) AF: 0.00127 AC: 575 AN: 451560

Other (OTH) AF: 0.000931 AC: 34 AN: 36528

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

African (AFR) AF: 0.000168 AC: 7 AN: 41586

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000787 Hom.: 0

Bravo AF: 0.000748

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.86
PhyloP100		0.92
PromoterAI		0.061	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs551554693; hg19: chr17-7487042;