chr6-43225580-G-T

Position:

• chr6-43225580-G-T

Variant summary

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

The NM_006443.3(DNPH1):​c.*153C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 785,980 control chromosomes in the GnomAD database, including 187 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 0.023 (54 hom., cov: 32)
  • Exomes 𝑓: 0.018 (133 hom.)
• Consequence: DNPH1 NM_006443.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

Genes affected

DNPH1 (HGNC:21218): (2'-deoxynucleoside 5'-phosphate N-hydrolase 1) This gene was identified on the basis of its stimulation by c-Myc protein. The latter is a transcription factor that participates in the regulation of cell proliferation, differentiation, and apoptosis. The exact function of this gene is not known but studies in rat suggest a role in cellular proliferation and c-Myc-mediated transformation. Two alternative transcripts encoding different proteins have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0231 (3517/152236) while in subpopulation AFR AF= 0.0399 (1656/41520). AF 95% confidence interval is 0.0383. There are 54 homozygotes in gnomad4. There are 1595 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNPH1	NM_006443.3	c.*153C>A		downstream_gene_variant		ENST00000230431.11	NP_006434.1
DNPH1	NM_199184.2	c.*382C>A		downstream_gene_variant			NP_954653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNPH1	ENST00000230431.11	c.*153C>A		downstream_gene_variant		1	NM_006443.3	ENSP00000230431.7

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3492 AN: 152118 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0183 AC: 11574 AN: 633744 Hom.: 133 Cov.: 9 AF XY: 0.0180 AC XY: 5863 AN XY: 326284

Gnomad4 AFR exome AF: 0.0379

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.0131

Gnomad4 SAS exome AF: 0.00993

Gnomad4 FIN exome AF: 0.00272

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0231 AC: 3517 AN: 152236 Hom.: 54 Cov.: 32 AF XY: 0.0214 AC XY: 1595 AN XY: 74454

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0232 Hom.: 10

Bravo AF: 0.0250

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115842765; hg19: chr6-43193318;