20-50935242-T-TAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_003859.3(DPM1):​c.679-7_679-6insTTT variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0770
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]
ADNP-AS1 (HGNC:51227): (ADNP antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 20-50935242-T-TAAA is Benign according to our data. Variant chr20-50935242-T-TAAA is described in ClinVar as [Benign]. Clinvar id is 464506.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000422 (60/1420506) while in subpopulation AFR AF= 0.00156 (48/30844). AF 95% confidence interval is 0.00121. There are 0 homozygotes in gnomad4_exome. There are 21 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DPM1NM_003859.3 linkuse as main transcriptc.679-7_679-6insTTT splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000371588.10
ADNP-AS1NR_110008.1 linkuse as main transcriptn.149+3793_149+3794insAAA intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPM1ENST00000371588.10 linkuse as main transcriptc.679-7_679-6insTTT splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_003859.3 P1
ADNP-AS1ENST00000558899.2 linkuse as main transcriptn.149+3793_149+3794insAAA intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
AF:
0.0000422
AC:
60
AN:
1420506
Hom.:
0
Cov.:
21
AF XY:
0.0000296
AC XY:
21
AN XY:
709186
show subpopulations
Gnomad4 AFR exome
AF:
0.00156
Gnomad4 AMR exome
AF:
0.0000460
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000556
Gnomad4 OTH exome
AF:
0.0000340
GnomAD4 genome
Cov.:
29

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
Benign, criteria provided, single submitterclinical testingInvitaeJul 25, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11480415; hg19: chr20-49551779; API