5-36241541-C-T

Variant names:

• chr5-36241541-C-T
• rs6891700
• NM_001085411.3:c.258G>A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001085411.3(NADK2):​c.258G>A​(p.Arg86Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,569,272 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (811 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (681 hom.)
• Consequence: NADK2 NM_001085411.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.414

Genes affected

NADK2 (HGNC:26404): (NAD kinase 2, mitochondrial) This gene encodes a mitochondrial kinase that catalyzes the phosphorylation of NAD to yield NADP. Mutations in this gene result in 2,4-dienoyl-CoA reductase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 5-36241541-C-T is Benign according to our data. Variant chr5-36241541-C-T is described in ClinVar as [Benign]. Clinvar id is 380097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.414 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK2	NM_001085411.3	c.258G>A	p.Arg86Arg	synonymous_variant	Exon 1 of 12	ENST00000381937.9	NP_001078880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADK2	ENST00000381937.9	c.258G>A	p.Arg86Arg	synonymous_variant	Exon 1 of 12	2	NM_001085411.3	ENSP00000371362.4

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8553 AN: 151956 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0412

GnomAD3 exomes AF: 0.0124 AC: 2276 AN: 184008 Hom.: 163 AF XY: 0.0106 AC XY: 1091 AN XY: 102986

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.00814

Gnomad ASJ exome AF: 0.00589

Gnomad EAS exome AF: 0.0000762

Gnomad SAS exome AF: 0.0132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000746

Gnomad OTH exome AF: 0.00614

GnomAD4 exome AF: 0.00641 AC: 9087 AN: 1417198 Hom.: 681 Cov.: 31 AF XY: 0.00612 AC XY: 4306 AN XY: 703838

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.00935

Gnomad4 ASJ exome AF: 0.00751

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000355

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0565 AC: 8594 AN: 152074 Hom.: 811 Cov.: 32 AF XY: 0.0545 AC XY: 4055 AN XY: 74376

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0209 Hom.: 56

Bravo AF: 0.0636

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Dec 22, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Progressive encephalopathy with leukodystrophy due to DECR deficiency Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs6891700; hg19: chr5-36241643;