17-41987883-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003315.4(DNAJC7):​c.946G>T​(p.Asp316Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DNAJC7
NM_003315.4 missense

Scores

8
10
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAJC7NM_003315.4 linkuse as main transcriptc.946G>T p.Asp316Tyr missense_variant 9/14 ENST00000457167.9 NP_003306.3 Q99615-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAJC7ENST00000457167.9 linkuse as main transcriptc.946G>T p.Asp316Tyr missense_variant 9/141 NM_003315.4 ENSP00000406463.2 Q99615-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 03, 2022The c.946G>T (p.D316Y) alteration is located in exon 9 (coding exon 9) of the DNAJC7 gene. This alteration results from a G to T substitution at nucleotide position 946, causing the aspartic acid (D) at amino acid position 316 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.77
D;.;.
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.99
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;.;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Uncertain
0.50
D
MutationAssessor
Pathogenic
4.5
H;.;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-7.5
D;D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.87
MutPred
0.61
Loss of disorder (P = 0.1305);.;.;
MVP
0.64
MPC
1.8
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.92
gMVP
0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40139901; API