chr20-50935242-T-TAAA

Position:

• chr20-50935242-T-TAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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

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
DPM1	NM_003859.3	c.679-7_679-6insTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371588.10
ADNP-AS1	NR_110008.1	n.149+3793_149+3794insAAA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPM1	ENST00000371588.10	c.679-7_679-6insTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003859.3	P1
ADNP-AS1	ENST00000558899.2	n.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

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

Submissions by phenotype

Congenital disorder of glycosylation type 1E Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11480415; hg19: chr20-49551779;