chr5-140647863-C-T

Variant names:

• chr5-140647863-C-T
• rs139482464
• NM_006083.4:c.-46C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.296
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1205148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 24 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IK	NM_006083.4	MANE Select	c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	NP_006074.2	Q13123
	IK	NM_006083.4	MANE Select	c.-46C>T		5_prime_UTR	Exon 1 of 20	NP_006074.2	Q13123
	MIR3655	NR_037428.1		n.20C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IK	ENST00000417647.7	TSL:1 MANE Select	c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000396301.2	Q13123
	IK	ENST00000417647.7	TSL:1 MANE Select	c.-46C>T		5_prime_UTR	Exon 1 of 20	ENSP00000396301.2	Q13123
	IK	ENST00000947150.1		c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000617209.1

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 512 AN: 152152 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00338 AC: 843 AN: 249290 AF XY: 0.00339

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 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

African (AFR) AF: 0.000478 AC: 16 AN: 33452

American (AMR) AF: 0.00134 AC: 60 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 33 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00256 AC: 221 AN: 86218

European-Finnish (FIN) AF: 0.00345 AC: 184 AN: 53402

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.00545 AC: 6055 AN: 1110368

Other (OTH) AF: 0.00317 AC: 191 AN: 60316

GnomAD4 genome AF: 0.00336 AC: 512 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.00322 AC XY: 240 AN XY: 74448

African (AFR) AF: 0.000650 AC: 27 AN: 41548

American (AMR) AF: 0.00314 AC: 48 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00377 AC: 40 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00557 AC: 379 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00338 Hom.: 1

Bravo AF: 0.00293

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.85
PhyloP100		0.30
PromoterAI		0.058	Neutral
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs139482464; hg19: chr5-140027448;