chr15-49654175-G-A

Variant names:

• chr15-49654175-G-A
• rs10519235
• NM_001144955.2:c.*10597G>A

Variant summary

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

The NM_001144955.2(DTWD1):​c.*10597G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 152,100 control chromosomes in the GnomAD database, including 1,337 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 0.080 (1337 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: -0.562
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTWD1	NM_001144955.2	c.*10597G>A		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.*10597G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001144955.2	ENSP00000385399.3
DTWD1	ENST00000251250.7	c.*10597G>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000251250.6

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12096 AN: 151982 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0441

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0799 AC: 12152 AN: 152100 Hom.: 1337 Cov.: 32 AF XY: 0.0768 AC XY: 5709 AN XY: 74360

African (AFR) AF: 0.247 AC: 10244 AN: 41494

American (AMR) AF: 0.0281 AC: 429 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5148

South Asian (SAS) AF: 0.0300 AC: 145 AN: 4826

European-Finnish (FIN) AF: 0.00641 AC: 68 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0169 AC: 1150 AN: 67978

Other (OTH) AF: 0.0436 AC: 92 AN: 2108

Alfa AF: 0.0629 Hom.: 129

Bravo AF: 0.0890

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.21
PhyloP100		-0.56
Mutation Taster		=99/1	polymorphism

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: rs10519235; hg19: chr15-49946372;