rs749987764

Variant names:

• chr20-50935113-A-T
• rs749987764
• NM_003859.3:c.*19T>A

Your query was ambiguous. Multiple possible variants found:

• chr20-50935113-A-T
• chr20-50935113-A-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_003859.3(DPM1):​c.*19T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,212,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: DPM1 NM_003859.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 20-50935113-A-T is Benign according to our data. Variant chr20-50935113-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 385237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000214 (26/1212174) while in subpopulation AMR AF = 0.000587 (26/44318). AF 95% confidence interval is 0.00041. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 17. This position passed quality control check.

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.*19T>A		3_prime_UTR	Exon 9 of 9	NP_003850.1	O60762
	DPM1	NM_001317034.1		c.*19T>A		3_prime_UTR	Exon 10 of 10	NP_001303963.1	O60762
	DPM1	NM_001317035.1		c.*19T>A		3_prime_UTR	Exon 10 of 10	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.*19T>A		3_prime_UTR	Exon 9 of 9	ENSP00000360644.5	O60762
	DPM1	ENST00000371582.8	TSL:1	c.*19T>A		3_prime_UTR	Exon 10 of 10	ENSP00000360638.4	Q5QPK2
	DPM1	ENST00000466152.5	TSL:1	n.*257T>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000507119.1	A0A804HIK9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000920 AC: 23 AN: 249980 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000669

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: 0.0000214 AC: 26 AN: 1212174 Hom.: 0 Cov.: 17 AF XY: 0.00000975 AC XY: 6 AN XY: 615202

African (AFR) AF: 0.00 AC: 0 AN: 28572

American (AMR) AF: 0.000587 AC: 26 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24612

East Asian (EAS) AF: 0.00 AC: 0 AN: 38378

South Asian (SAS) AF: 0.00 AC: 0 AN: 80748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4046

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 886232

Other (OTH) AF: 0.00 AC: 0 AN: 51952

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.71
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749987764; hg19: chr20-49551650;