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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003859.3. 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
	DPM1	NM_003859.3	MANE Select	c.679-7A>T		splice_region intron	N/A	NP_003850.1	O60762
	DPM1	NM_001317034.1		c.784-7A>T		splice_region intron	N/A	NP_001303963.1	O60762
	DPM1	NM_001317035.1		c.760-7A>T		splice_region intron	N/A	NP_001303964.1	Q5QPK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPM1	ENST00000371588.10	TSL:1 MANE Select	c.679-7A>T		splice_region intron	N/A	ENSP00000360644.5	O60762
	DPM1	ENST00000371582.8	TSL:1	c.760-7A>T		splice_region intron	N/A	ENSP00000360638.4	Q5QPK2
	DPM1	ENST00000466152.5	TSL:1	n.*134-7A>T		splice_region intron	N/A	ENSP00000507119.1	A0A804HIK9

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Congenital disorder of glycosylation type 1E (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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;