17-42017395-C-G

Variant summary

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

The ENST00000307641(NKIRAS2):​c.-246C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000261 in 1,456,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

NKIRAS2
ENST00000307641 5_prime_UTR_premature_start_codon_gain

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.51
Variant links:
Genes affected
NKIRAS2 (HGNC:17898): (NFKB inhibitor interacting Ras like 2) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; regulation of signal transduction; and surfactant homeostasis. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.328247).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAJC7NM_003315.4 linkc.22G>C p.Asp8His missense_variant Exon 1 of 14 ENST00000457167.9 NP_003306.3 Q99615-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAJC7ENST00000457167.9 linkc.22G>C p.Asp8His missense_variant Exon 1 of 14 1 NM_003315.4 ENSP00000406463.2 Q99615-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000204
AC:
5
AN:
244696
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133478
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:
0.0000446
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000261
AC:
38
AN:
1456978
Hom.:
0
Cov.:
31
AF XY:
0.0000221
AC XY:
16
AN XY:
725078
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:
0.0000342
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000248
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T;.
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.1
L;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.8
N;.
REVEL
Benign
0.25
Sift
Uncertain
0.0030
D;.
Sift4G
Uncertain
0.0050
D;.
Polyphen
1.0
D;.
Vest4
0.63
MutPred
0.41
Loss of disorder (P = 0.0393);Loss of disorder (P = 0.0393);
MVP
0.54
MPC
0.78
ClinPred
0.42
T
GERP RS
5.3
Varity_R
0.42
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs782649180; hg19: chr17-40169413; API