chr15-40767189-T-C

Variant names:

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

Variant summary

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

The NM_018163.3(DNAJC17):​c.*751A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,457,468 control chromosomes in the GnomAD database, including 1,869 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 0.069 (526 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1343 hom.)
• Consequence: DNAJC17 NM_018163.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC17	NM_018163.3	MANE Select	c.*751A>G		3_prime_UTR	Exon 11 of 11	NP_060633.1
	GCHFR	NM_005258.3	MANE Select	c.132-37T>C		intron	N/A	NP_005249.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10388 AN: 151534 Hom.: 524 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0737

GnomAD2 exomes AF: 0.0456 AC: 6562 AN: 143918 AF XY: 0.0443

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0298

Gnomad ASJ exome AF: 0.0563

Gnomad EAS exome AF: 0.0215

Gnomad FIN exome AF: 0.0235

Gnomad NFE exome AF: 0.0396

Gnomad OTH exome AF: 0.0473

GnomAD4 exome AF: 0.0405 AC: 52863 AN: 1305818 Hom.: 1343 Cov.: 30 AF XY: 0.0408 AC XY: 25964 AN XY: 637010

African (AFR) AF: 0.136 AC: 3642 AN: 26726

American (AMR) AF: 0.0369 AC: 875 AN: 23738

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 1227 AN: 19544

East Asian (EAS) AF: 0.0286 AC: 918 AN: 32072

South Asian (SAS) AF: 0.0611 AC: 3754 AN: 61490

European-Finnish (FIN) AF: 0.0247 AC: 1218 AN: 49330

Middle Eastern (MID) AF: 0.0908 AC: 475 AN: 5234

European-Non Finnish (NFE) AF: 0.0369 AC: 38169 AN: 1034030

Other (OTH) AF: 0.0482 AC: 2585 AN: 53654

GnomAD4 genome AF: 0.0686 AC: 10406 AN: 151650 Hom.: 526 Cov.: 33 AF XY: 0.0668 AC XY: 4954 AN XY: 74202

African (AFR) AF: 0.140 AC: 5737 AN: 40952

American (AMR) AF: 0.0564 AC: 862 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 232 AN: 3468

East Asian (EAS) AF: 0.0261 AC: 135 AN: 5174

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4828

European-Finnish (FIN) AF: 0.0220 AC: 233 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2555 AN: 68008

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0596 Hom.: 135

Bravo AF: 0.0731

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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;