10-21930627-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.223-1486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,024 control chromosomes in the GnomAD database, including 27,456 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 0.57 (27456 hom., cov: 31)
• Consequence: DNAJC1 NM_022365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC1	NM_022365.4	c.223-1486A>G		intron_variant		ENST00000376980.8
DNAJC1	XM_011519614.4	c.223-1486A>G		intron_variant
DNAJC1	XM_017016536.3	c.223-1486A>G		intron_variant
DNAJC1	XM_047425628.1	c.223-1486A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC1	ENST00000376980.8	c.223-1486A>G		intron_variant		1	NM_022365.4	P1
DNAJC1	ENST00000476103.3	c.223-1486A>G		intron_variant, NMD_transcript_variant		2
DNAJC1	ENST00000376946.2	n.558-1486A>G		intron_variant, non_coding_transcript_variant		3
DNAJC1	ENST00000447548.5	n.188-1486A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87109 AN: 151906 Hom.: 27452 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.563

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.573 AC: 87128 AN: 152024 Hom.: 27456 Cov.: 31 AF XY: 0.579 AC XY: 43041 AN XY: 74302

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.564

Alfa AF: 0.646 Hom.: 53641

Bravo AF: 0.553

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.9
Dann	Benign	0.62

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: rs2666750; hg19: chr10-22219556; COSMIC: COSV63283771; COSMIC: COSV63283771;