15-49623209-T-C

Variant names:

• chr15-49623209-T-C
• rs17402569
• NM_001144955.2:c.-55-1904T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000403028.8(DTWD1):​c.-55-1904T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,188 control chromosomes in the GnomAD database, including 3,134 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 0.18 (3134 hom., cov: 32)
• Consequence: DTWD1 ENST00000403028.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000403028.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTWD1	NM_001144955.2	MANE Select	c.-55-1904T>C		intron	N/A	NP_001138427.1
	DTWD1	NM_020234.6		c.-183-462T>C		intron	N/A	NP_064619.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTWD1	ENST00000403028.8	TSL:1 MANE Select	c.-55-1904T>C		intron	N/A	ENSP00000385399.3
	DTWD1	ENST00000251250.7	TSL:1	c.-183-462T>C		intron	N/A	ENSP00000251250.6
	DTWD1	ENST00000557968.5	TSL:1	n.-55-1904T>C		intron	N/A	ENSP00000452628.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27783 AN: 152070 Hom.: 3137 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.182 AC: 27768 AN: 152188 Hom.: 3134 Cov.: 32 AF XY: 0.184 AC XY: 13720 AN XY: 74396

African (AFR) AF: 0.0602 AC: 2503 AN: 41560

American (AMR) AF: 0.171 AC: 2608 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3466

East Asian (EAS) AF: 0.00481 AC: 25 AN: 5194

South Asian (SAS) AF: 0.172 AC: 829 AN: 4822

European-Finnish (FIN) AF: 0.315 AC: 3326 AN: 10564

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.249 AC: 16914 AN: 67986

Other (OTH) AF: 0.198 AC: 418 AN: 2106

Alfa AF: 0.209 Hom.: 490

Bravo AF: 0.166

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		-0.052
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17402569; hg19: chr15-49915406;