20-50935242-T-TAA

Variant names:

• chr20-50935242-T-TAA
• rs11480415
• NM_003859.3:c.679-7_679-6insTT

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_679-6insTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,543,996 control chromosomes in the GnomAD database, including 95 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (82 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (13 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-TAA is Benign according to our data. Variant chr20-50935242-T-TAA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0872 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_679-6insTT		splice_region intron	N/A	NP_003850.1	O60762
	DPM1	NM_001317034.1		c.784-7_784-6insTT		splice_region intron	N/A	NP_001303963.1	O60762
	DPM1	NM_001317035.1		c.760-7_760-6insTT		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_679-6insTT		splice_region intron	N/A	ENSP00000360644.5	O60762
	DPM1	ENST00000371582.8	TSL:1	c.760-7_760-6insTT		splice_region intron	N/A	ENSP00000360638.4	Q5QPK2
	DPM1	ENST00000466152.5	TSL:1	n.*134-7_*134-6insTT		splice_region intron	N/A	ENSP00000507119.1	A0A804HIK9

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 2676 AN: 124312 Hom.: 79 Cov.: 29

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00722

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0144

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.0138

GnomAD2 exomes AF: 0.00355 AC: 835 AN: 235258 AF XY: 0.00249

Gnomad AFR exome AF: 0.0549

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000745

Gnomad EAS exome AF: 0.000288

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00177 AC: 2515 AN: 1419624 Hom.: 13 Cov.: 21 AF XY: 0.00151 AC XY: 1071 AN XY: 708782

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

African (AFR) AF: 0.0609 AC: 1851 AN: 30394

American (AMR) AF: 0.00272 AC: 118 AN: 43400

Ashkenazi Jewish (ASJ) AF: 0.000429 AC: 11 AN: 25654

East Asian (EAS) AF: 0.000229 AC: 9 AN: 39316

South Asian (SAS) AF: 0.000320 AC: 27 AN: 84300

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53330

Middle Eastern (MID) AF: 0.00288 AC: 16 AN: 5560

European-Non Finnish (NFE) AF: 0.000262 AC: 283 AN: 1078866

Other (OTH) AF: 0.00337 AC: 198 AN: 58804

⚠️ 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: 0.0216 AC: 2684 AN: 124372 Hom.: 82 Cov.: 29 AF XY: 0.0208 AC XY: 1264 AN XY: 60738

African (AFR) AF: 0.0901 AC: 2544 AN: 28238

American (AMR) AF: 0.00722 AC: 93 AN: 12884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3112

East Asian (EAS) AF: 0.00 AC: 0 AN: 4514

South Asian (SAS) AF: 0.000229 AC: 1 AN: 4362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8676

Middle Eastern (MID) AF: 0.0152 AC: 4 AN: 264

European-Non Finnish (NFE) AF: 0.000301 AC: 18 AN: 59756

Other (OTH) AF: 0.0136 AC: 24 AN: 1762

Alfa AF: 0.000830 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	DPM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11480415; hg19: chr20-49551779;