rs4227

Variant names:

• chr17-7587859-G-T
• rs4227
• NM_004870.4:c.*308G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7587859-G-T
• chr17-7587859-G-A

Variant summary

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

The NM_004870.4(MPDU1):​c.*308G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 520,342 control chromosomes in the GnomAD database, including 134,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35439 hom., cov: 32)
  • Exomes 𝑓: 0.73 (99355 hom.)
• Consequence: MPDU1 NM_004870.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.325
• Publications: 66 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 Gene-Disease associations (from GenCC):

• MPDU1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-7587859-G-T is Benign according to our data. Variant chr17-7587859-G-T is described in ClinVar as Benign. ClinVar VariationId is 325524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004870.4. 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_004870.4	MANE Select	c.*308G>T		3_prime_UTR	Exon 7 of 7	NP_004861.2	A0A0S2Z4W8
	MPDU1	NM_001330073.1		c.*415G>T		3_prime_UTR	Exon 6 of 6	NP_001317002.1	J3QW43
	MPDU1	NR_024603.1		n.1263G>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	ENST00000250124.11	TSL:1 MANE Select	c.*308G>T		3_prime_UTR	Exon 7 of 7	ENSP00000250124.6	O75352-1
	MPDU1	ENST00000853390.1		c.*308G>T		3_prime_UTR	Exon 7 of 7	ENSP00000523449.1
	MPDU1	ENST00000853388.1		c.*308G>T		3_prime_UTR	Exon 7 of 7	ENSP00000523447.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103073 AN: 151902 Hom.: 35419 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.680

GnomAD2 exomes AF: 0.715 AC: 95351 AN: 133404 AF XY: 0.729

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.795

Gnomad EAS exome AF: 0.774

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.727

Gnomad OTH exome AF: 0.740

GnomAD4 exome AF: 0.730 AC: 268921 AN: 368322 Hom.: 99355 Cov.: 2 AF XY: 0.742 AC XY: 152388 AN XY: 205490

African (AFR) AF: 0.575 AC: 6358 AN: 11054

American (AMR) AF: 0.567 AC: 16544 AN: 29182

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 10771 AN: 13572

East Asian (EAS) AF: 0.804 AC: 11828 AN: 14714

South Asian (SAS) AF: 0.832 AC: 50140 AN: 60274

European-Finnish (FIN) AF: 0.690 AC: 11450 AN: 16588

Middle Eastern (MID) AF: 0.789 AC: 1253 AN: 1588

European-Non Finnish (NFE) AF: 0.726 AC: 147108 AN: 202748

Other (OTH) AF: 0.724 AC: 13469 AN: 18602

GnomAD4 genome AF: 0.678 AC: 103130 AN: 152020 Hom.: 35439 Cov.: 32 AF XY: 0.682 AC XY: 50651 AN XY: 74316

African (AFR) AF: 0.576 AC: 23856 AN: 41440

American (AMR) AF: 0.623 AC: 9508 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2750 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3992 AN: 5164

South Asian (SAS) AF: 0.836 AC: 4036 AN: 4826

European-Finnish (FIN) AF: 0.696 AC: 7358 AN: 10578

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49353 AN: 67962

Other (OTH) AF: 0.682 AC: 1435 AN: 2104

Alfa AF: 0.718 Hom.: 173337

Bravo AF: 0.666

Asia WGS AF: 0.773 AC: 2686 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MPDU1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.80
PhyloP100		-0.33
Mutation Taster		=100/0	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: rs4227; hg19: chr17-7491177; COSMIC: COSV51469439; COSMIC: COSV51469439;