Genetic Variant NM_003859.3:c.679-7_679-6insTTT (chr20-50935242-T-TAAA) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_003859.3(DPM1):c.679-7_679-6insTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,420,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

DPM1
NM_003859.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0770

Publications

3 publications found

Variant links:

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]

DPM1 links:

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

ADNP-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 20-50935242-T-TAAA is Benign according to our data. Variant chr20-50935242-T-TAAA is described in ClinVar as Benign. ClinVar VariationId is 464506.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPM1	NM_003859.3 link	c.679-7_679-6insTTT		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000371588.10	NP_003850.1	O60762A0A0S2Z4Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPM1	ENST00000371588.10 link	c.679-7_679-6insTTT		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_003859.3	ENSP00000360644.5		O60762

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000468

AC:

AN:

235258

AF XY:

0.0000234

show subpopulations

Gnomad AFR exome

AF:

0.000759

Gnomad AMR exome

AF:

0.0000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000422

AC:

AN:

1420506

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

709186

show subpopulations

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

African (AFR)

AF:

0.00156

AC:

AN:

30844

American (AMR)

AF:

0.0000460

AC:

AN:

43474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25668

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

84352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00000556

AC:

AN:

1079066

Other (OTH)

AF:

0.0000340

AC:

AN:

58868

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.303

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation type 1E

Benign:1

Jul 25, 2023

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

PhyloP100

-0.077

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over