rs10519989

Variant names:

• chr15-35238372-G-T
• rs10519989
• ENST00000560386.5:n.201-17790C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000560386.5(DPH6):​n.201-17790C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 152,082 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.026 (74 hom., cov: 32)
• Consequence: DPH6 ENST00000560386.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• Publications: 1 publications found

Genes affected

DPH6 (HGNC:30543): (diphthamine biosynthesis 6) Enables diphthine-ammonia ligase activity. Predicted to be involved in peptidyl-diphthamide biosynthetic process from peptidyl-histidine. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293367 (HGNC:):

ANP32AP1 (HGNC:42949): (acidic nuclear phosphoprotein 32 family member A pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0264 (4010/152082) while in subpopulation NFE AF = 0.0397 (2701/68010). AF 95% confidence interval is 0.0385. There are 74 homozygotes in GnomAd4. There are 1941 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPH6	XM_017022708.3	c.751-17790C>A		intron_variant	Intron 8 of 8		XP_016878197.1
DPH6	XM_047433263.1	c.*35+66521C>A		intron_variant	Intron 9 of 9		XP_047289219.1
DPH6	XR_001751412.3	n.680-17790C>A		intron_variant	Intron 7 of 7
ANP32AP1	NR_003144.2	n.*175G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPH6	ENST00000560386.5	n.201-17790C>A		intron_variant	Intron 3 of 3	1
ENSG00000293367	ENST00000560832.1	n.*175G>T		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4012 AN: 151976 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00665

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00788

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0264 AC: 4010 AN: 152082 Hom.: 74 Cov.: 32 AF XY: 0.0261 AC XY: 1941 AN XY: 74344

African (AFR) AF: 0.00661 AC: 274 AN: 41472

American (AMR) AF: 0.0271 AC: 414 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00789 AC: 38 AN: 4818

European-Finnish (FIN) AF: 0.0414 AC: 437 AN: 10546

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2701 AN: 68010

Other (OTH) AF: 0.0261 AC: 55 AN: 2110

Alfa AF: 0.0356 Hom.: 143

Bravo AF: 0.0247

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.43
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs10519989; hg19: chr15-35530573;