Genetic Variant NM_022365.4:c.820+29A>T (chr10-21904493-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022365.4(DNAJC1):c.820+29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAJC1
NM_022365.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.573

Publications

11 publications found

Variant links:

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]

DNAJC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJC1	NM_022365.4 link	c.820+29A>T	intron_variant	Intron 7 of 11	ENST00000376980.8	NP_071760.2	Q96KC8
DNAJC1	XM_011519614.4 link	c.820+29A>T	intron_variant	Intron 7 of 9		XP_011517916.1
DNAJC1	XM_017016536.3 link	c.820+29A>T	intron_variant	Intron 7 of 8		XP_016872025.1
DNAJC1	XM_047425628.1 link	c.820+29A>T	intron_variant	Intron 7 of 9		XP_047281584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8 link	c.820+29A>T		intron_variant	Intron 7 of 11	1	NM_022365.4	ENSP00000366179.3		Q96KC8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1151974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

580586

African (AFR)

AF:

0.00

AC:

AN:

24774

American (AMR)

AF:

0.00

AC:

AN:

27790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21282

East Asian (EAS)

AF:

0.00

AC:

AN:

35868

South Asian (SAS)

AF:

0.00

AC:

AN:

62594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4832

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

876048

Other (OTH)

AF:

0.00

AC:

AN:

48664

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.010

(source)

DANN

Benign

0.59

PhyloP100

-0.57

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over