rs60224379

Variant names:

• chr20-50935243-T-A
• rs60224379
• NM_003859.3:c.679-7A>T

Variant summary

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

The NM_003859.3(DPM1):​c.679-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,376,748 control chromosomes in the GnomAD database, including 4,058 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2136 hom., cov: 29)
  • Exomes 𝑓: 0.027 (1922 hom.)
• Consequence: DPM1 NM_003859.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002757
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0770
• Publications: 2 publications found

Genes affected

DPM1 (HGNC:3005): (dolichyl-phosphate mannosyltransferase subunit 1, catalytic) Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. Human DPM1 lacks a carboxy-terminal transmembrane domain and signal sequence and is regulated by DPM2. Mutations in this gene are associated with congenital disorder of glycosylation type Ie. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ADNP-AS1 (HGNC:51227): (ADNP antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-50935243-T-A is Benign according to our data. Variant chr20-50935243-T-A is described in ClinVar as Benign. ClinVar VariationId is 94380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPM1	NM_003859.3	c.679-7A>T		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000371588.10	NP_003850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPM1	ENST00000371588.10	c.679-7A>T		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_003859.3	ENSP00000360644.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15399 AN: 148044 Hom.: 2123 Cov.: 29

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0449

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0839

GnomAD2 exomes AF: 0.0508 AC: 9513 AN: 187132 AF XY: 0.0448

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.0641

Gnomad EAS exome AF: 0.0355

Gnomad FIN exome AF: 0.0153

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0389

GnomAD4 exome AF: 0.0267 AC: 32822 AN: 1228624 Hom.: 1922 Cov.: 21 AF XY: 0.0256 AC XY: 15824 AN XY: 616974

African (AFR) AF: 0.350 AC: 9837 AN: 28100

American (AMR) AF: 0.0337 AC: 1335 AN: 39628

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 1118 AN: 23002

East Asian (EAS) AF: 0.0209 AC: 740 AN: 35406

South Asian (SAS) AF: 0.0299 AC: 2268 AN: 75762

European-Finnish (FIN) AF: 0.0133 AC: 644 AN: 48516

Middle Eastern (MID) AF: 0.0323 AC: 158 AN: 4896

European-Non Finnish (NFE) AF: 0.0156 AC: 14415 AN: 921552

Other (OTH) AF: 0.0446 AC: 2307 AN: 51762

GnomAD4 genome AF: 0.104 AC: 15437 AN: 148124 Hom.: 2136 Cov.: 29 AF XY: 0.101 AC XY: 7312 AN XY: 72054

African (AFR) AF: 0.315 AC: 12839 AN: 40802

American (AMR) AF: 0.0474 AC: 705 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 156 AN: 3430

East Asian (EAS) AF: 0.0261 AC: 133 AN: 5094

South Asian (SAS) AF: 0.0333 AC: 156 AN: 4684

European-Finnish (FIN) AF: 0.0163 AC: 153 AN: 9372

Middle Eastern (MID) AF: 0.0486 AC: 14 AN: 288

European-Non Finnish (NFE) AF: 0.0167 AC: 1110 AN: 66650

Other (OTH) AF: 0.0837 AC: 171 AN: 2044

Alfa AF: 0.0462 Hom.: 168

Bravo AF: 0.114

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 28, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 15, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Congenital disorder of glycosylation type 1E Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.046
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: rs60224379; hg19: chr20-49551780;