chr15-40767189-T-A

Variant names:

• chr15-40767189-T-A
• rs2301176
• NM_018163.3:c.*751A>T

Variant summary

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

The NM_018163.3(DNAJC17):​c.*751A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,306,280 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: DNAJC17 NM_018163.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 0 publications found

Genes affected

DNAJC17 (HGNC:25556): (DnaJ heat shock protein family (Hsp40) member C17) Predicted to enable RNA binding activity. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II and toxin transport. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GCHFR (HGNC:4194): (GTP cyclohydrolase I feedback regulator) GTP cyclohydrolase I feedback regulatory protein binds to and mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase I. The regulatory protein, GCHFR, consists of a homodimer. It is postulated that GCHFR may play a role in regulating phenylalanine metabolism in the liver and in the production of biogenic amine neurotransmitters and nitric oxide. [provided by RefSeq, Jul 2008]

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=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC17	NM_018163.3	c.*751A>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000220496.9	NP_060633.1
GCHFR	NM_005258.3	c.132-37T>A		intron_variant	Intron 2 of 2	ENST00000260447.6	NP_005249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC17	ENST00000220496.9	c.*751A>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_018163.3	ENSP00000220496.4
GCHFR	ENST00000260447.6	c.132-37T>A		intron_variant	Intron 2 of 2	1	NM_005258.3	ENSP00000260447.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.66e-7 AC: 1 AN: 1306280 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 637230

African (AFR) AF: 0.00 AC: 0 AN: 26750

American (AMR) AF: 0.00 AC: 0 AN: 23744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19548

East Asian (EAS) AF: 0.00 AC: 0 AN: 32072

South Asian (SAS) AF: 0.00 AC: 0 AN: 61538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5234

European-Non Finnish (NFE) AF: 9.67e-7 AC: 1 AN: 1034386

Other (OTH) AF: 0.00 AC: 0 AN: 53672

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-0.21

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: rs2301176; hg19: chr15-41059387;