5-140647863-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006083.4(IK):​c.-46C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,612,330 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0046 ( 24 hom. )

Consequence

IK
NM_006083.4 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.296
Variant links:
Genes affected
IK (HGNC:5958): (IK cytokine) The protein encoded by this gene was identified by its RED repeat, a stretch of repeated arginine, glutamic acid and aspartic acid residues. The protein localizes to discrete dots within the nucleus, excluding the nucleolus. Its function is unknown. This gene maps to chromosome 5; however, a pseudogene may exist on chromosome 2. [provided by RefSeq, Jul 2008]
MIR3655 (HGNC:38960): (microRNA 3655) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
NDUFA2 (HGNC:7685): (NADH:ubiquinone oxidoreductase subunit A2) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane, and may be involved in regulating complex I activity or its assembly via assistance in redox processes. Mutations in this gene are associated with Leigh syndrome, an early-onset progressive neurodegenerative disorder. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 5-140647863-C-T is Benign according to our data. Variant chr5-140647863-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1205148.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 24 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IKNM_006083.4 linkc.-46C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 20 ENST00000417647.7 NP_006074.2 Q13123Q95HA6Q9UK43
IKNM_006083.4 linkc.-46C>T 5_prime_UTR_variant Exon 1 of 20 ENST00000417647.7 NP_006074.2 Q13123Q95HA6Q9UK43
NDUFA2NM_002488.5 linkc.-280G>A upstream_gene_variant ENST00000252102.9 NP_002479.1 O43678-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IKENST00000417647 linkc.-46C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 20 1 NM_006083.4 ENSP00000396301.2 Q13123
IKENST00000417647 linkc.-46C>T 5_prime_UTR_variant Exon 1 of 20 1 NM_006083.4 ENSP00000396301.2 Q13123
NDUFA2ENST00000252102.9 linkc.-280G>A upstream_gene_variant 1 NM_002488.5 ENSP00000252102.5 O43678-1

Frequencies

GnomAD3 genomes
AF:
0.00337
AC:
512
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000652
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00314
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00557
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00338
AC:
843
AN:
249290
Hom.:
4
AF XY:
0.00339
AC XY:
459
AN XY:
135232
show subpopulations
Gnomad AFR exome
AF:
0.000645
Gnomad AMR exome
AF:
0.00122
Gnomad ASJ exome
AF:
0.00109
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00258
Gnomad FIN exome
AF:
0.00288
Gnomad NFE exome
AF:
0.00548
Gnomad OTH exome
AF:
0.00314
GnomAD4 exome
AF:
0.00463
AC:
6767
AN:
1460060
Hom.:
24
Cov.:
31
AF XY:
0.00471
AC XY:
3419
AN XY:
726432
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00134
Gnomad4 ASJ exome
AF:
0.00126
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00256
Gnomad4 FIN exome
AF:
0.00345
Gnomad4 NFE exome
AF:
0.00545
Gnomad4 OTH exome
AF:
0.00317
GnomAD4 genome
AF:
0.00336
AC:
512
AN:
152270
Hom.:
0
Cov.:
32
AF XY:
0.00322
AC XY:
240
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.000650
Gnomad4 AMR
AF:
0.00314
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00377
Gnomad4 NFE
AF:
0.00557
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00338
Hom.:
1
Bravo
AF:
0.00293
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 19, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.0
DANN
Benign
0.85

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: rs139482464; hg19: chr5-140027448; API