NM_001144955.2:c.-55-655T>G

Variant names:

• chr15-49624458-T-G
• rs925104
• NM_001144955.2:c.-55-655T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144955.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTWD1	NM_001144955.2	MANE Select	c.-55-655T>G		intron	N/A	NP_001138427.1
	DTWD1	NM_020234.6		c.-55-655T>G		intron	N/A	NP_064619.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTWD1	ENST00000403028.8	TSL:1 MANE Select	c.-55-655T>G		intron	N/A	ENSP00000385399.3
	DTWD1	ENST00000251250.7	TSL:1	c.-55-655T>G		intron	N/A	ENSP00000251250.6
	DTWD1	ENST00000557968.5	TSL:1	n.-55-655T>G		intron	N/A	ENSP00000452628.1

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

African (AFR) AF: 0.0833 AC: 3459 AN: 41520

American (AMR) AF: 0.246 AC: 3765 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3472

East Asian (EAS) AF: 0.183 AC: 948 AN: 5186

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4832

European-Finnish (FIN) AF: 0.285 AC: 3020 AN: 10584

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23514 AN: 67956

Other (OTH) AF: 0.262 AC: 551 AN: 2106

Alfa AF: 0.279 Hom.: 886

Bravo AF: 0.239

Asia WGS AF: 0.177 AC: 616 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.67
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs925104; hg19: chr15-49916655;