7-73682967-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_032317.3(DNAJC30):​c.457G>T​(p.Ala153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,606,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

DNAJC30
NM_032317.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275
Variant links:
Genes affected
DNAJC30 (HGNC:16410): (DnaJ heat shock protein family (Hsp40) member C30) This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a chain DnaJ homolog subfamily C member 30, mitochondrial (size 187) in uniprot entity DJC30_HUMAN there are 9 pathogenic changes around while only 1 benign (90%) in NM_032317.3
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07179925).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAJC30NM_032317.3 linkuse as main transcriptc.457G>T p.Ala153Ser missense_variant 1/1 ENST00000395176.3 NP_115693.2 Q96LL9B3KSU4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAJC30ENST00000395176.3 linkuse as main transcriptc.457G>T p.Ala153Ser missense_variant 1/16 NM_032317.3 ENSP00000378605.1 Q96LL9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152254
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000124
AC:
3
AN:
241858
Hom.:
0
AF XY:
0.00000757
AC XY:
1
AN XY:
132178
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000279
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000474
AC:
69
AN:
1454628
Hom.:
0
Cov.:
55
AF XY:
0.0000443
AC XY:
32
AN XY:
722450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000596
Gnomad4 OTH exome
AF:
0.0000500
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152254
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000825
AC:
1

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 GeneticsFeb 28, 2024The c.457G>T (p.A153S) alteration is located in exon 1 (coding exon 1) of the DNAJC30 gene. This alteration results from a G to T substitution at nucleotide position 457, causing the alanine (A) at amino acid position 153 to be replaced by a serine (S). 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
Benign
0.073
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
5.1
DANN
Benign
0.90
DEOGEN2
Benign
0.018
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.033
Sift
Benign
0.41
T
Sift4G
Benign
0.51
T
Polyphen
0.068
B
Vest4
0.17
MutPred
0.20
Gain of phosphorylation at A153 (P = 0.0227);
MVP
0.29
MPC
0.40
ClinPred
0.047
T
GERP RS
-1.0
Varity_R
0.055
gMVP
0.34

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782689807; hg19: chr7-73097297; API