NM_021800.3:c.*142A>G

Variant names:

• chr10-67796974-T-C
• rs41299238
• NM_021800.3:c.*142A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021800.3(DNAJC12):​c.*142A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 543,888 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (222 hom., cov: 32)
  • Exomes 𝑓: 0.042 (454 hom.)
• Consequence: DNAJC12 NM_021800.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.193
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-67796974-T-C is Benign according to our data. Variant chr10-67796974-T-C is described in ClinVar as Benign. ClinVar VariationId is 1286374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

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.*142A>G		3_prime_UTR	Exon 5 of 5	NP_068572.1	Q9UKB3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC12	ENST00000225171.7	TSL:1 MANE Select	c.*142A>G		3_prime_UTR	Exon 5 of 5	ENSP00000225171.2	Q9UKB3-1
	DNAJC12	ENST00000857833.1		c.*142A>G		3_prime_UTR	Exon 3 of 3	ENSP00000527892.1
	DNAJC12	ENST00000857834.1		c.*142A>G		3_prime_UTR	Exon 3 of 3	ENSP00000527893.1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7925 AN: 152142 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0575

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0421 AC: 16494 AN: 391628 Hom.: 454 Cov.: 6 AF XY: 0.0429 AC XY: 8647 AN XY: 201464

African (AFR) AF: 0.0774 AC: 804 AN: 10388

American (AMR) AF: 0.0384 AC: 438 AN: 11410

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 855 AN: 11508

East Asian (EAS) AF: 0.000150 AC: 4 AN: 26658

South Asian (SAS) AF: 0.0572 AC: 1348 AN: 23560

European-Finnish (FIN) AF: 0.0365 AC: 1354 AN: 37134

Middle Eastern (MID) AF: 0.0953 AC: 289 AN: 3032

European-Non Finnish (NFE) AF: 0.0422 AC: 10375 AN: 245874

Other (OTH) AF: 0.0465 AC: 1027 AN: 22064

GnomAD4 genome AF: 0.0521 AC: 7929 AN: 152260 Hom.: 222 Cov.: 32 AF XY: 0.0506 AC XY: 3765 AN XY: 74452

African (AFR) AF: 0.0780 AC: 3242 AN: 41540

American (AMR) AF: 0.0467 AC: 714 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0582 AC: 281 AN: 4828

European-Finnish (FIN) AF: 0.0359 AC: 381 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2827 AN: 68018

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

Alfa AF: 0.0558 Hom.: 136

Bravo AF: 0.0543

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs41299238; hg19: chr10-69556732;