10-21904493-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022365.4(DNAJC1):c.820+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,301,460 control chromosomes in the GnomAD database, including 328,885 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 0.66 (33391 hom., cov: 31)
  • Exomes 𝑓: 0.71 (295494 hom.)
• Consequence: DNAJC1 NM_022365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

Genes affected

DNAJC1 (HGNC:20090): (DnaJ heat shock protein family (Hsp40) member C1) The membrane protein encoded by this gene is a DNAJ-like heat shock protein that binds the molecular chaperone BiP. In addition, the encoded protein contains two SANT domains that have been shown to bind serpin alpha1-antichymotrypsin and inter-alpha trypsin inhibitor heavy chain 4. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC1	NM_022365.4	c.820+29A>G		intron_variant		ENST00000376980.8
DNAJC1	XM_011519614.4	c.820+29A>G		intron_variant
DNAJC1	XM_017016536.3	c.820+29A>G		intron_variant
DNAJC1	XM_047425628.1	c.820+29A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC1	ENST00000376980.8	c.820+29A>G		intron_variant		1	NM_022365.4	P1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99540 AN: 151748 Hom.: 33380 Cov.: 31

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.631

GnomAD3 exomes AF: 0.712 AC: 134007 AN: 188232 Hom.: 48711 AF XY: 0.716 AC XY: 74221 AN XY: 103728

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.702

Gnomad ASJ exome AF: 0.541

Gnomad EAS exome AF: 0.988

Gnomad SAS exome AF: 0.792

Gnomad FIN exome AF: 0.711

Gnomad NFE exome AF: 0.692

Gnomad OTH exome AF: 0.686

GnomAD4 exome AF: 0.713 AC: 819316 AN: 1149594 Hom.: 295494 Cov.: 14 AF XY: 0.714 AC XY: 413864 AN XY: 579430

Gnomad4 AFR exome AF: 0.537

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.790

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.656 AC: 99578 AN: 151866 Hom.: 33391 Cov.: 31 AF XY: 0.660 AC XY: 48978 AN XY: 74198

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.633

Alfa AF: 0.670 Hom.: 13901

Bravo AF: 0.644

Asia WGS AF: 0.839 AC: 2896 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.012
Dann	Benign	0.72

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: rs792455; hg19: chr10-22193422;