5-43609170-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182977.3(NNT):c.-26T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,583,958 control chromosomes in the GnomAD database, including 79,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5432 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73911 hom.)
• Consequence: NNT NM_182977.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.312

Genes affected

NNT (HGNC:7863): (nicotinamide nucleotide transhydrogenase) This gene encodes an integral protein of the inner mitochondrial membrane. The enzyme couples hydride transfer between NAD(H) and NADP(+) to proton translocation across the inner mitochondrial membrane. Under most physiological conditions, the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH. The resulting NADPH is used for biosynthesis and in free radical detoxification. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-43609170-T-C is Benign according to our data. Variant chr5-43609170-T-C is described in ClinVar as [Benign]. Clinvar id is 1325907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NNT	NM_182977.3	c.-26T>C		5_prime_UTR_variant	2/22	ENST00000344920.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NNT	ENST00000344920.9	c.-26T>C		5_prime_UTR_variant	2/22	1	NM_182977.3	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36113 AN: 151920 Hom.: 5434 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.263 AC: 63154 AN: 240306 Hom.: 9702 AF XY: 0.273 AC XY: 35337 AN XY: 129600

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.0641

Gnomad SAS exome AF: 0.243

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.313 AC: 447802 AN: 1431920 Hom.: 73911 Cov.: 28 AF XY: 0.312 AC XY: 221368 AN XY: 709486

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.0956

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.237 AC: 36103 AN: 152038 Hom.: 5432 Cov.: 32 AF XY: 0.236 AC XY: 17517 AN XY: 74334

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.273

Alfa AF: 0.301 Hom.: 6228

Bravo AF: 0.224

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glucocorticoid deficiency 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.8
Dann	Benign	0.64

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: rs12187908; hg19: chr5-43609272; COSMIC: COSV52925486; COSMIC: COSV52925486;