10-67805532-A-G

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.502+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,535,888 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (136 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (89 hom.)
• Consequence: DNAJC12 NM_021800.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305

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=-0.87).
• BP6: Variant 10-67805532-A-G is Benign according to our data. Variant chr10-67805532-A-G is described in ClinVar as [Benign]. Clinvar id is 1280177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC12	NM_021800.3	c.502+51T>C		intron_variant		ENST00000225171.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC12	ENST00000225171.7	c.502+51T>C		intron_variant		1	NM_021800.3	P1
DNAJC12	ENST00000483798.6	c.592+51T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3445 AN: 151858 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00867

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0168

GnomAD3 exomes AF: 0.00654 AC: 1323 AN: 202140 Hom.: 47 AF XY: 0.00474 AC XY: 519 AN XY: 109602

Gnomad AFR exome AF: 0.0795

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000488

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.00218

GnomAD4 exome AF: 0.00204 AC: 2825 AN: 1383912 Hom.: 89 Cov.: 25 AF XY: 0.00184 AC XY: 1261 AN XY: 686056

Gnomad4 AFR exome AF: 0.0776

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000382

Gnomad4 OTH exome AF: 0.00516

GnomAD4 genome AF: 0.0227 AC: 3451 AN: 151976 Hom.: 136 Cov.: 32 AF XY: 0.0212 AC XY: 1578 AN XY: 74282

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.00865

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0119 Hom.: 3

Bravo AF: 0.0261

Asia WGS AF: 0.00404 AC: 14 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

Apr 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.4
Dann	Benign	0.60

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: rs77971812; hg19: chr10-69565290;