17-7583790-A-G

Variant names:

• chr17-7583790-A-G
• rs2075230
• NM_001330073.1:c.-73A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330073.1(MPDU1):​c.-73A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,478,702 control chromosomes in the GnomAD database, including 24,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3689 hom., cov: 34)
  • Exomes 𝑓: 0.17 (20792 hom.)
• Consequence: MPDU1 NM_001330073.1 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.244
• Publications: 37 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-7583790-A-G is Benign according to our data. Variant chr17-7583790-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 325511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

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.-73A>G		5_prime_UTR	Exon 1 of 6	NP_001317002.1
	MPDU1	NR_024603.1		n.144A>G		non_coding_transcript_exon	Exon 1 of 7
	MPDU1-AS1	NR_136401.2		n.175+128T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	ENST00000582151.1	TSL:6	c.-73A>G		5_prime_UTR	Exon 1 of 1	ENSP00000462500.1
	MPDU1	ENST00000572936.5	TSL:5	n.-73A>G		non_coding_transcript_exon	Exon 1 of 7	ENSP00000459306.1
	MPDU1-AS1	ENST00000687005.2		n.309T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31441 AN: 152158 Hom.: 3680 Cov.: 34

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.194 AC: 48110 AN: 248430 AF XY: 0.188

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.353

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.167 AC: 222155 AN: 1326426 Hom.: 20792 Cov.: 20 AF XY: 0.168 AC XY: 111690 AN XY: 666726

African (AFR) AF: 0.296 AC: 9097 AN: 30698

American (AMR) AF: 0.197 AC: 8799 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3619 AN: 25340

East Asian (EAS) AF: 0.394 AC: 15368 AN: 39048

South Asian (SAS) AF: 0.201 AC: 16820 AN: 83582

European-Finnish (FIN) AF: 0.204 AC: 10479 AN: 51410

Middle Eastern (MID) AF: 0.150 AC: 784 AN: 5242

European-Non Finnish (NFE) AF: 0.149 AC: 147736 AN: 990542

Other (OTH) AF: 0.169 AC: 9453 AN: 55988

GnomAD4 genome AF: 0.207 AC: 31479 AN: 152276 Hom.: 3689 Cov.: 34 AF XY: 0.210 AC XY: 15657 AN XY: 74458

African (AFR) AF: 0.294 AC: 12231 AN: 41558

American (AMR) AF: 0.197 AC: 3013 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1831 AN: 5184

South Asian (SAS) AF: 0.198 AC: 958 AN: 4830

European-Finnish (FIN) AF: 0.201 AC: 2136 AN: 10604

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10247 AN: 68018

Other (OTH) AF: 0.190 AC: 401 AN: 2108

Alfa AF: 0.165 Hom.: 3094

Bravo AF: 0.211

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		-0.24
PromoterAI		-0.028	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075230; hg19: chr17-7487108; COSMIC: COSV51467852; COSMIC: COSV51467852;