Genetic Variant DNAJC7:p.Asp316Asn (chr17-41987883-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_003315.4(DNAJC7):c.946G>A(p.Asp316Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D316Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DNAJC7
NM_003315.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

0 publications found

Variant links:

Genes affected

DNAJC7 (HGNC:12392): (DnaJ heat shock protein family (Hsp40) member C7) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the chaperone proteins heat shock proteins 70 and 90 in an ATP-dependent manner and may function as a co-chaperone. Pseudogenes of this gene are found on chromosomes 1 and 6. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

DNAJC7 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

DNAJC7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.79

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003315.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC7	NM_003315.4	MANE Select	c.946G>A	p.Asp316Asn	missense	Exon 9 of 14	NP_003306.3	Q99615-1
DNAJC7	NM_001144766.3		c.778G>A	p.Asp260Asn	missense	Exon 9 of 14	NP_001138238.1	Q99615-2
DNAJC7	NR_029431.2		n.880G>A		non_coding_transcript_exon	Exon 8 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC7	ENST00000457167.9	TSL:1 MANE Select	c.946G>A	p.Asp316Asn	missense	Exon 9 of 14	ENSP00000406463.2	Q99615-1
DNAJC7	ENST00000316603.12	TSL:1	c.778G>A	p.Asp260Asn	missense	Exon 8 of 13	ENSP00000313311.7	Q99615-2
DNAJC7	ENST00000589810.5	TSL:1	n.*11G>A		non_coding_transcript_exon	Exon 9 of 10	ENSP00000467477.1	K7EPP7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

245856

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.060

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.11

MutationAssessor

Pathogenic

3.8

PhyloP100

7.6

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

Sift4G

Benign

0.070

Polyphen

0.99

Vest4

0.79

MutPred

0.58

Gain of MoRF binding (P = 0.2893)

MVP

0.68

MPC

1.6

ClinPred

0.99

GERP RS

5.8

Varity_R

0.67

gMVP

0.67

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over