rs16924888

Variant names:

• chr10-67815814-G-A
• rs16924888
• NM_021800.3:c.158-4151C>T

Variant summary

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

The NM_021800.3(DNAJC12):​c.158-4151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,114 control chromosomes in the GnomAD database, including 1,207 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 0.12 (1207 hom., cov: 32)
• Consequence: DNAJC12 NM_021800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 4 publications found

Genes affected

DNAJC12 (HGNC:28908): (DnaJ heat shock protein family (Hsp40) member C12) This gene encodes a member of a subclass of the HSP40/DnaJ protein family. Members of this family of proteins are associated with complex assembly, protein folding, and export. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DNAJC12 Gene-Disease associations (from GenCC):

• hyperphenylalaninemia due to DNAJC12 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC12	NM_021800.3	c.158-4151C>T		intron_variant	Intron 2 of 4	ENST00000225171.7	NP_068572.1
DNAJC12	NM_201262.2	c.158-4151C>T		intron_variant	Intron 2 of 2		NP_957714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC12	ENST00000225171.7	c.158-4151C>T		intron_variant	Intron 2 of 4	1	NM_021800.3	ENSP00000225171.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18076 AN: 151996 Hom.: 1205 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18087 AN: 152114 Hom.: 1207 Cov.: 32 AF XY: 0.118 AC XY: 8760 AN XY: 74348

African (AFR) AF: 0.119 AC: 4949 AN: 41504

American (AMR) AF: 0.0853 AC: 1302 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3466

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.169 AC: 816 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1229 AN: 10550

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8730 AN: 68004

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.127 Hom.: 868

Bravo AF: 0.116

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.23
PhyloP100		-0.10
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: rs16924888; hg19: chr10-69575572;