ENST00000557968.5:n.-24G>A

Variant names:

• chr15-49621013-T-A
• NM_152647.3:c.-386A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000557968.5(DTWD1):​n.-165T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DTWD1 ENST00000557968.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.80
• Publications: 0 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.-386A>T		upstream_gene_variant		ENST00000299338.11	NP_689860.2
DTWD1	NM_001144955.2	c.-165T>A		upstream_gene_variant		ENST00000403028.8	NP_001138427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.-386A>T		upstream_gene_variant		2	NM_152647.3	ENSP00000299338.6
DTWD1	ENST00000403028.8	c.-165T>A		upstream_gene_variant		1	NM_001144955.2	ENSP00000385399.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0020
DANN	Benign	0.63
PhyloP100		-5.8
PromoterAI		0.26	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr15-49913210;