10-21885612-C-T

Position:

• chr10-21885612-C-T

Variant summary

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

The NM_022365.4(DNAJC1):​c.821-3173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,988 control chromosomes in the GnomAD database, including 31,296 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 0.63 (31296 hom., cov: 33)
• Consequence: DNAJC1 NM_022365.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC1	NM_022365.4	c.821-3173G>A		intron_variant		ENST00000376980.8	NP_071760.2
DNAJC1	XM_011519614.4	c.821-3173G>A		intron_variant			XP_011517916.1
DNAJC1	XM_017016536.3	c.821-3173G>A		intron_variant			XP_016872025.1
DNAJC1	XM_047425628.1	c.821-3173G>A		intron_variant			XP_047281584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8	c.821-3173G>A		intron_variant		1	NM_022365.4	ENSP00000366179	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95932 AN: 151870 Hom.: 31288 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.631 AC: 95961 AN: 151988 Hom.: 31296 Cov.: 33 AF XY: 0.636 AC XY: 47225 AN XY: 74282

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.594

Alfa AF: 0.651 Hom.: 7970

Bravo AF: 0.618

Asia WGS AF: 0.817 AC: 2842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
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: rs792456; hg19: chr10-22174541;