chr15-49624458-T-G

Position:

• chr15-49624458-T-G

Variant summary

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

The NM_001144955.2(DTWD1):​c.-55-655T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,148 control chromosomes in the GnomAD database, including 5,695 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 0.25 (5695 hom., cov: 32)
• Consequence: DTWD1 NM_001144955.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTWD1	NM_001144955.2	c.-55-655T>G		intron_variant		ENST00000403028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTWD1	ENST00000403028.8	c.-55-655T>G		intron_variant		1	NM_001144955.2	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37983 AN: 152030 Hom.: 5694 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.250 AC: 37966 AN: 152148 Hom.: 5695 Cov.: 32 AF XY: 0.247 AC XY: 18369 AN XY: 74378

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.262

Alfa AF: 0.287 Hom.: 883

Bravo AF: 0.239

Asia WGS AF: 0.177 AC: 616 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs925104; hg19: chr15-49916655;