10-21930627-T-C

Variant names:

• chr10-21930627-T-C
• rs2666750
• NM_022365.4:c.223-1486A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAJC1	NM_022365.4	c.223-1486A>G		intron_variant	Intron 1 of 11	ENST00000376980.8	NP_071760.2
DNAJC1	XM_011519614.4	c.223-1486A>G		intron_variant	Intron 1 of 9		XP_011517916.1
DNAJC1	XM_017016536.3	c.223-1486A>G		intron_variant	Intron 1 of 8		XP_016872025.1
DNAJC1	XM_047425628.1	c.223-1486A>G		intron_variant	Intron 1 of 9		XP_047281584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8	c.223-1486A>G		intron_variant	Intron 1 of 11	1	NM_022365.4	ENSP00000366179.3
DNAJC1	ENST00000376946.2	n.558-1486A>G		intron_variant	Intron 1 of 2	3
DNAJC1	ENST00000447548.5	n.188-1486A>G		intron_variant	Intron 1 of 3	5
DNAJC1	ENST00000476103.3	n.223-1486A>G		intron_variant	Intron 1 of 3	2		ENSP00000431248.1

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

African (AFR) AF: 0.305 AC: 12624 AN: 41452

American (AMR) AF: 0.606 AC: 9249 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3472

East Asian (EAS) AF: 0.957 AC: 4939 AN: 5162

South Asian (SAS) AF: 0.761 AC: 3670 AN: 4824

European-Finnish (FIN) AF: 0.692 AC: 7312 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45812 AN: 67954

Other (OTH) AF: 0.564 AC: 1191 AN: 2112

Alfa AF: 0.638 Hom.: 126818

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
PhyloP100		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: rs2666750; hg19: chr10-22219556; COSMIC: COSV63283771; COSMIC: COSV63283771;