rs2301176

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-40767189-T-A
• chr15-40767189-T-C

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018163.3. 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
	DNAJC17	NM_018163.3	MANE Select	c.*751A>T		3_prime_UTR	Exon 11 of 11	NP_060633.1	Q9NVM6
	GCHFR	NM_005258.3	MANE Select	c.132-37T>A		intron	N/A	NP_005249.1	P30047-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC17	ENST00000220496.9	TSL:1 MANE Select	c.*751A>T		3_prime_UTR	Exon 11 of 11	ENSP00000220496.4	Q9NVM6
	GCHFR	ENST00000260447.6	TSL:1 MANE Select	c.132-37T>A		intron	N/A	ENSP00000260447.4	P30047-1
	GCHFR	ENST00000559445.1	TSL:1	c.99-37T>A		intron	N/A	ENSP00000453871.1	P30047-2

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2301176;

hg19: chr15-41059387;