rs10997823

Variant names:

• chr10-67827950-A-T
• rs10997823
• NM_021800.3:c.79-4558T>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.79-4558T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,998 control chromosomes in the GnomAD database, including 41,299 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 0.73 (41299 hom., cov: 30)
• Consequence: DNAJC12 NM_021800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC12	NM_021800.3	c.79-4558T>A		intron_variant	Intron 1 of 4	ENST00000225171.7	NP_068572.1
DNAJC12	NM_201262.2	c.79-4558T>A		intron_variant	Intron 1 of 2		NP_957714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC12	ENST00000225171.7	c.79-4558T>A		intron_variant	Intron 1 of 4	1	NM_021800.3	ENSP00000225171.2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110867 AN: 151880 Hom.: 41272 Cov.: 30

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.730 AC: 110942 AN: 151998 Hom.: 41299 Cov.: 30 AF XY: 0.720 AC XY: 53508 AN XY: 74288

African (AFR) AF: 0.693 AC: 28706 AN: 41428

American (AMR) AF: 0.709 AC: 10814 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2857 AN: 3468

East Asian (EAS) AF: 0.277 AC: 1431 AN: 5164

South Asian (SAS) AF: 0.602 AC: 2902 AN: 4822

European-Finnish (FIN) AF: 0.694 AC: 7328 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54585 AN: 67976

Other (OTH) AF: 0.744 AC: 1572 AN: 2114

Alfa AF: 0.773 Hom.: 5711

Bravo AF: 0.724

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0060
DANN	Benign	0.66
PhyloP100		-2.7
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: rs10997823; hg19: chr10-69587708;