15-49647649-C-T

Variant names:

• chr15-49647649-C-T
• rs8039808
• NM_001144955.2:c.*4071C>T

Variant summary

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

The NM_001144955.2(DTWD1):​c.*4071C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 152,064 control chromosomes in the GnomAD database, including 1,176 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 0.076 (1176 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: 0.0340

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTWD1	NM_001144955.2	c.*4071C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000403028.8	NP_001138427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTWD1	ENST00000403028.8	c.*4071C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001144955.2	ENSP00000385399.3
DTWD1	ENST00000251250.7	c.*4071C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000251250.6

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11453 AN: 151946 Hom.: 1172 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0407

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0756 AC: 11498 AN: 152064 Hom.: 1176 Cov.: 32 AF XY: 0.0725 AC XY: 5393 AN XY: 74340

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0208 Hom.: 50

Bravo AF: 0.0847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.53

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: rs8039808; hg19: chr15-49939846;