17-7587061-G-T

Position:

• chr17-7587061-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_004870.4(MPDU1):​c.507+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,451,758 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000028 (0 hom., cov: 20)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: MPDU1 NM_004870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000214 (28/1306510) while in subpopulation EAS AF= 0.000362 (14/38682). AF 95% confidence interval is 0.000218. There are 0 homozygotes in gnomad4_exome. There are 15 alleles in male gnomad4_exome subpopulation. Median coverage is 22. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDU1	NM_004870.4	c.507+44G>T		intron_variant		ENST00000250124.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDU1	ENST00000250124.11	c.507+44G>T		intron_variant		1	NM_004870.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000275 AC: 4 AN: 145248 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000692

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000208

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000246 AC: 6 AN: 243620 Hom.: 0 AF XY: 0.0000301 AC XY: 4 AN XY: 132680

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000166

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000913

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000214 AC: 28 AN: 1306510 Hom.: 0 Cov.: 22 AF XY: 0.0000229 AC XY: 15 AN XY: 656202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000362

Gnomad4 SAS exome AF: 0.0000241

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000103

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome AF: 0.0000275 AC: 4 AN: 145248 Hom.: 0 Cov.: 20 AF XY: 0.0000142 AC XY: 1 AN XY: 70342

Gnomad4 AFR AF: 0.0000255

Gnomad4 AMR AF: 0.0000692

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302661; hg19: chr17-7490379;