rs10519989

Positions:

• chr15-35238372-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000560386.5(DPH6):​n.201-17790C>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPH6	XM_017022708.3	c.751-17790C>A		intron_variant			XP_016878197.1
DPH6	XM_047433263.1	c.*35+66521C>A		intron_variant			XP_047289219.1
DPH6	XR_001751412.3	n.680-17790C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPH6	ENST00000560386.5	n.201-17790C>A		intron_variant, non_coding_transcript_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

Gnomad4 AFR AF: 0.00661

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00789

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0304 Hom.: 7

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519989; hg19: chr15-35530573;