rs10519235

chr15-49654175-G-A

Variant summary

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

The NM_001144955.2(DTWD1):c.*10597G>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 0.0799 in 152,100 control chromosomes in the GnomAD database, including 1,337 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 0.080 (1337 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DTWD1 NM_001144955.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562

Genes affected

DTWD1 (HGNC:30926): (DTW domain containing 1) Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in tRNA modification. Located in nucleus. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTWD1	NM_001144955.2	c.*10597G>A		3_prime_UTR_variant	5/5	ENST00000403028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTWD1	ENST00000403028.8	c.*10597G>A		3_prime_UTR_variant	5/5	1	NM_001144955.2	P1
DTWD1	ENST00000251250.7	c.*10597G>A		3_prime_UTR_variant	6/6	1		P1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12096 AN: 151982 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0441

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0799 AC: 12152 AN: 152100 Hom.: 1337 Cov.: 32 AF XY: 0.0768 AC XY: 5709 AN XY: 74360

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0281

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0573 Hom.: 108

Bravo AF: 0.0890

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.42
Dann	Benign	0.21

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: rs10519235; hg19: chr15-49946372;