rs2236215

chr1-15565920-A-Cchr1-15565920-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015291.4(DNAJC16):c.1600A>C(p.Arg534=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,612,318 control chromosomes in the GnomAD database, including 58,765 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (10668 hom., cov: 30)
  • Exomes 𝑓: 0.25 (48097 hom.)
• Consequence: DNAJC16 NM_015291.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0007144
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

Genes affected

DNAJC16 (HGNC:29157): (DnaJ heat shock protein family (Hsp40) member C16) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC16	NM_015291.4	c.1600A>C	p.Arg534=	splice_region_variant, synonymous_variant	12/15	ENST00000375847.8
DNAJC16	NM_001287811.2	c.664A>C	p.Arg222=	splice_region_variant, synonymous_variant	11/14
DNAJC16	NR_109898.2	n.1729A>C		splice_region_variant, non_coding_transcript_exon_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC16	ENST00000375847.8	c.1600A>C	p.Arg534=	splice_region_variant, synonymous_variant	12/15	1	NM_015291.4	P1
	ENST00000606186.1	n.37T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51199 AN: 151548 Hom.: 10632 Cov.: 30

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.312

GnomAD3 exomes AF: 0.246 AC: 61871 AN: 251038 Hom.: 9140 AF XY: 0.244 AC XY: 33055 AN XY: 135714

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.0655

Gnomad SAS exome AF: 0.221

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.248 AC: 361884 AN: 1460652 Hom.: 48097 Cov.: 32 AF XY: 0.247 AC XY: 179223 AN XY: 726752

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.0773

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.338 AC: 51280 AN: 151666 Hom.: 10668 Cov.: 30 AF XY: 0.334 AC XY: 24777 AN XY: 74100

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0650

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.308

Alfa AF: 0.266 Hom.: 5560

Bravo AF: 0.343

Asia WGS AF: 0.175 AC: 606 AN: 3478

EpiCase AF: 0.253

EpiControl AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00071
dbscSNV1_RF	Benign	0.0040
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

Publications

LitVar

Other links and lift over

dbSNP: rs2236215; hg19: chr1-15892415; COSMIC: COSV65448320; COSMIC: COSV65448320;