NM_003859.3:c.679-7_679-6insT

Variant names:

• chr20-50935242-T-TA
• rs11480415
• NM_003859.3:c.679-7_679-6insT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003859.3(DPM1):​c.679-7_679-6insT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,541,218 control chromosomes in the GnomAD database, including 1,645 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1377 hom., cov: 29)
  • Exomes 𝑓: 0.019 (268 hom.)
• Consequence: DPM1 NM_003859.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0770
• Publications: 3 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 -16 ACMG points.

• BP6: Variant 20-50935242-T-TA is Benign according to our data. Variant chr20-50935242-T-TA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 338752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 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.679-7_679-6insT		splice_region intron	N/A	NP_003850.1	O60762
	DPM1	NM_001317034.1		c.784-7_784-6insT		splice_region intron	N/A	NP_001303963.1	O60762
	DPM1	NM_001317035.1		c.760-7_760-6insT		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.679-7_679-6insT		splice_region intron	N/A	ENSP00000360644.5	O60762
	DPM1	ENST00000371582.8	TSL:1	c.760-7_760-6insT		splice_region intron	N/A	ENSP00000360638.4	Q5QPK2
	DPM1	ENST00000466152.5	TSL:1	n.*134-7_*134-6insT		splice_region intron	N/A	ENSP00000507119.1	A0A804HIK9

Frequencies

GnomAD3 genomes AF: 0.102 AC: 12651 AN: 124268 Hom.: 1369 Cov.: 29

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0360

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0831

GnomAD2 exomes AF: 0.0298 AC: 7020 AN: 235258 AF XY: 0.0263

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.0222

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.0251

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0219

GnomAD4 exome AF: 0.0189 AC: 26737 AN: 1416894 Hom.: 268 Cov.: 21 AF XY: 0.0184 AC XY: 13012 AN XY: 707286

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.215 AC: 6501 AN: 30266

American (AMR) AF: 0.0238 AC: 1028 AN: 43224

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 968 AN: 25438

East Asian (EAS) AF: 0.0170 AC: 669 AN: 39238

South Asian (SAS) AF: 0.0226 AC: 1898 AN: 83828

European-Finnish (FIN) AF: 0.0102 AC: 540 AN: 53160

Middle Eastern (MID) AF: 0.0213 AC: 118 AN: 5548

European-Non Finnish (NFE) AF: 0.0122 AC: 13112 AN: 1077508

Other (OTH) AF: 0.0324 AC: 1903 AN: 58684

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.102 AC: 12678 AN: 124324 Hom.: 1377 Cov.: 29 AF XY: 0.0991 AC XY: 6013 AN XY: 60704

African (AFR) AF: 0.363 AC: 10233 AN: 28202

American (AMR) AF: 0.0471 AC: 607 AN: 12882

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 156 AN: 3112

East Asian (EAS) AF: 0.0293 AC: 132 AN: 4512

South Asian (SAS) AF: 0.0355 AC: 155 AN: 4362

European-Finnish (FIN) AF: 0.0172 AC: 149 AN: 8670

Middle Eastern (MID) AF: 0.0379 AC: 10 AN: 264

European-Non Finnish (NFE) AF: 0.0182 AC: 1090 AN: 59752

Other (OTH) AF: 0.0828 AC: 146 AN: 1764

Alfa AF: 0.0143 Hom.: 2

ClinVar

ClinVar submissions

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)
-	-	1	Congenital disorder of glycosylation type 1E (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.077
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: rs11480415; hg19: chr20-49551779; COSMIC: COSV65373423; COSMIC: COSV65373423;