rs1035794099

Variant names:

• chr10-67811606-C-G
• rs1035794099
• NM_021800.3:c.215G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-67811606-C-G
• chr10-67811606-C-A
• chr10-67811606-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_021800.3(DNAJC12):​c.215G>C​(p.Arg72Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC12 NM_021800.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.92
• 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), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981
• PP5: Variant 10-67811606-C-G is Pathogenic according to our data. Variant chr10-67811606-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 393302.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021800.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC12	NM_021800.3	MANE Select	c.215G>C	p.Arg72Pro	missense	Exon 3 of 5	NP_068572.1	Q9UKB3-1
	DNAJC12	NM_201262.2		c.215G>C	p.Arg72Pro	missense	Exon 3 of 3	NP_957714.1	Q9UKB3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC12	ENST00000225171.7	TSL:1 MANE Select	c.215G>C	p.Arg72Pro	missense	Exon 3 of 5	ENSP00000225171.2	Q9UKB3-1
	DNAJC12	ENST00000339758.7	TSL:1	c.215G>C	p.Arg72Pro	missense	Exon 3 of 3	ENSP00000343575.6	Q9UKB3-2
	DNAJC12	ENST00000483798.6	TSL:3	c.305G>C	p.Arg102Pro	missense	Exon 4 of 6	ENSP00000474215.1	S4R3E2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Hyperphenylalaninemia due to DNAJC12 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	4.2	H
PhyloP100		6.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.87		Loss of MoRF binding (P = 6e-04)
MVP		0.75
MPC		0.47
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.95
gMVP		0.88
Mutation Taster		=13/87	disease causing (ClinVar)

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: rs1035794099; hg19: chr10-69571364; COSMIC: COSV56550162; COSMIC: COSV56550162;