10-67806559-C-T

Variant names:

• chr10-67806559-C-T
• rs10997818
• NM_021800.3:c.298-772G>A

Variant summary

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

The NM_021800.3(DNAJC12):​c.298-772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,142 control chromosomes in the GnomAD database, including 2,388 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 0.17 (2388 hom., cov: 32)
• Consequence: DNAJC12 NM_021800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC12	NM_021800.3	c.298-772G>A		intron_variant	Intron 3 of 4	ENST00000225171.7	NP_068572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC12	ENST00000225171.7	c.298-772G>A		intron_variant	Intron 3 of 4	1	NM_021800.3	ENSP00000225171.2
DNAJC12	ENST00000483798.6	c.388-772G>A		intron_variant	Intron 4 of 5	3		ENSP00000474215.1
DNAJC12	ENST00000480963.5	n.*218-772G>A		intron_variant	Intron 4 of 4	2		ENSP00000473979.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25819 AN: 152024 Hom.: 2388 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.170 AC: 25846 AN: 152142 Hom.: 2388 Cov.: 32 AF XY: 0.168 AC XY: 12486 AN XY: 74362

African (AFR) AF: 0.245 AC: 10156 AN: 41486

American (AMR) AF: 0.169 AC: 2587 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.130 AC: 673 AN: 5174

South Asian (SAS) AF: 0.156 AC: 754 AN: 4830

European-Finnish (FIN) AF: 0.107 AC: 1130 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9645 AN: 68004

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.0837 Hom.: 98

Bravo AF: 0.177

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		0.44
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: rs10997818; hg19: chr10-69566317;