rs3210227

chr15-49625144-G-Achr15-49625144-G-T

Variant summary

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

The NM_001144955.2(DTWD1):c.-24G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,602,110 control chromosomes in the GnomAD database, including 50,386 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 0.19 (3510 hom., cov: 32)
  • Exomes 𝑓: 0.24 (46876 hom.)
• Consequence: DTWD1 NM_001144955.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTWD1	NM_001144955.2	c.-24G>A		5_prime_UTR_variant	2/5	ENST00000403028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTWD1	ENST00000403028.8	c.-24G>A		5_prime_UTR_variant	2/5	1	NM_001144955.2	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29420 AN: 151758 Hom.: 3513 Cov.: 32

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.209 AC: 51244 AN: 245284 Hom.: 6608 AF XY: 0.215 AC XY: 28690 AN XY: 133154

Gnomad AFR exome AF: 0.0592

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.245 AC: 354663 AN: 1450234 Hom.: 46876 Cov.: 31 AF XY: 0.245 AC XY: 176469 AN XY: 721164

Gnomad4 AFR exome AF: 0.0585

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.000936

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.194 AC: 29410 AN: 151876 Hom.: 3510 Cov.: 32 AF XY: 0.195 AC XY: 14483 AN XY: 74212

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.00503

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.208

Alfa AF: 0.249 Hom.: 1651

Bravo AF: 0.177

Asia WGS AF: 0.0770 AC: 267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3210227; hg19: chr15-49917341;