10-67796974-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.193

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1286374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC12	NM_021800.3	c.*142A>G		3_prime_UTR_variant	5/5	ENST00000225171.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC12	ENST00000225171.7	c.*142A>G		3_prime_UTR_variant	5/5	1	NM_021800.3	P1

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

Gnomad4 AFR exome AF: 0.0774

Gnomad4 AMR exome AF: 0.0384

Gnomad4 ASJ exome AF: 0.0743

Gnomad4 EAS exome AF: 0.000150

Gnomad4 SAS exome AF: 0.0572

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0422

Gnomad4 OTH exome AF: 0.0465

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

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.0467

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0582

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0468 Hom.: 46

Bravo AF: 0.0543

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.3
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs41299238; hg19: chr10-69556732;