Genetic Variant NNT:c.-26T>C (chr5-43609170-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.312

Variant links:

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]

NNT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
NNT	NM_182977.3 link	c.-26T>C		5_prime_UTR_variant	Exon 2 of 22	ENST00000344920.9	NP_892022.2	Q13423A0A024R0C3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNT	ENST00000344920 link	c.-26T>C		5_prime_UTR_variant	Exon 2 of 22	1	NM_182977.3	ENSP00000343873.4		Q13423

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36113

AN:

151920

Hom.:

5434

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.263

AC:

63154

AN:

240306

AF XY:

0.273

show subpopulations

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 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.:

AF XY:

0.312

AC XY:

221368

AN XY:

709486

show subpopulations

Gnomad4 AFR exome

AF:

0.0545

AC:

1780

AN:

32680

Gnomad4 AMR exome

AF:

0.188

AC:

7841

AN:

41808

Gnomad4 ASJ exome

AF:

0.372

AC:

9392

AN:

25252

Gnomad4 EAS exome

AF:

0.0956

AC:

3758

AN:

39320

Gnomad4 SAS exome

AF:

0.245

AC:

19945

AN:

81306

Gnomad4 FIN exome

AF:

0.343

AC:

18159

AN:

52944

Gnomad4 NFE exome

AF:

0.336

AC:

367020

AN:

1093750

Gnomad4 Remaining exome

AF:

0.304

AC:

17985

AN:

59200

Heterozygous variant carriers

13203

26407

39610

52814

66017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

11698

23396

35094

46792

58490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.237

AC:

36103

AN:

152038

Hom.:

5432

Cov.:

AF XY:

0.236

AC XY:

17517

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0631

AC:

0.0630698

AN:

0.0630698

Gnomad4 AMR

AF:

0.236

AC:

0.236177

AN:

0.236177

Gnomad4 ASJ

AF:

0.355

AC:

0.354551

AN:

0.354551

Gnomad4 EAS

AF:

0.0667

AC:

0.0666667

AN:

0.0666667

Gnomad4 SAS

AF:

0.233

AC:

0.233002

AN:

0.233002

Gnomad4 FIN

AF:

0.344

AC:

0.343661

AN:

0.343661

Gnomad4 NFE

AF:

0.332

AC:

0.332446

AN:

0.332446

Gnomad4 OTH

AF:

0.273

AC:

0.272986

AN:

0.272986

Heterozygous variant carriers

1335

2670

4004

5339

6674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.301

Hom.:

8121

Bravo

AF:

0.224

Asia WGS

AF:

0.152

AC:

529

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glucocorticoid deficiency 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.8

DANN

Benign

0.64

Mutation Taster

=100/0

polymorphism (auto)

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over