rs1037575

Positions:

• chr15-35448381-G-A
• chr15-35448381-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080650.4(DPH6):​c.505+2304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,052 control chromosomes in the GnomAD database, including 33,641 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 0.60 (33641 hom., cov: 32)
• Consequence: DPH6 NM_080650.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPH6	NM_080650.4	c.505+2304C>T		intron_variant		ENST00000256538.9	NP_542381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPH6	ENST00000256538.9	c.505+2304C>T		intron_variant		1	NM_080650.4	ENSP00000256538	P1
DPH6	ENST00000558266.5	c.133+2304C>T		intron_variant		5		ENSP00000454015
DPH6	ENST00000561411.1	c.361+2304C>T		intron_variant		4		ENSP00000453967
DPH6	ENST00000559784.5	n.347+6366C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91939 AN: 151934 Hom.: 33644 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.605 AC: 91936 AN: 152052 Hom.: 33641 Cov.: 32 AF XY: 0.614 AC XY: 45638 AN XY: 74326

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.626

Alfa AF: 0.755 Hom.: 50198

Bravo AF: 0.579

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1037575; hg19: chr15-35740582;