chr2-24951397-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016544.3(DNAJC27):​c.686C>T​(p.Ser229Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DNAJC27
NM_016544.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.55
Variant links:
Genes affected
DNAJC27 (HGNC:30290): (DnaJ heat shock protein family (Hsp40) member C27) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport and positive regulation of MAPK cascade. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34311777).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAJC27NM_016544.3 linkuse as main transcriptc.686C>T p.Ser229Leu missense_variant 6/7 ENST00000264711.7 NP_057628.1
DNAJC27XM_047444647.1 linkuse as main transcriptc.473C>T p.Ser158Leu missense_variant 6/7 XP_047300603.1
DNAJC27XM_047444648.1 linkuse as main transcriptc.473C>T p.Ser158Leu missense_variant 6/7 XP_047300604.1
DNAJC27NM_001198559.1 linkuse as main transcriptc.529-3649C>T intron_variant NP_001185488.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAJC27ENST00000264711.7 linkuse as main transcriptc.686C>T p.Ser229Leu missense_variant 6/71 NM_016544.3 ENSP00000264711 P1Q9NZQ0-1
DNAJC27ENST00000534855.5 linkuse as main transcriptc.529-3649C>T intron_variant 1 ENSP00000440086 Q9NZQ0-3
DNAJC27ENST00000380809.7 linkuse as main transcriptc.*554C>T 3_prime_UTR_variant, NMD_transcript_variant 8/92 ENSP00000370187 Q9NZQ0-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
32
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249110
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134660
show subpopulations
Gnomad AFR exome
AF:
0.0000618
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
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 GeneticsMay 23, 2023The c.686C>T (p.S229L) alteration is located in exon 6 (coding exon 6) of the DNAJC27 gene. This alteration results from a C to T substitution at nucleotide position 686, causing the serine (S) at amino acid position 229 to be replaced by a leucine (L). 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
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.22
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.018
D
Polyphen
0.19
B
Vest4
0.37
MVP
0.51
MPC
0.29
ClinPred
0.88
D
GERP RS
5.4
Varity_R
0.37
gMVP
0.63

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: rs373476031; hg19: chr2-25174266; API