Variant chr5-43609241-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182977.3(NNT):c.46C>T(p.Leu16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,613,168 control chromosomes in the GnomAD database, including 263,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 32681 hom., cov: 31)

Exomes 𝑓: 0.55 ( 230728 hom. )

Consequence

NNT
NM_182977.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.126

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-43609241-C-T is Benign according to our data. Variant chr5-43609241-C-T is described in ClinVar as [Benign]. Clinvar id is 1174913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-43609241-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.126 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NNT	NM_182977.3 linkuse as main transcript	c.46C>T	p.Leu16=	synonymous_variant	2/22	ENST00000344920.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NNT	ENST00000344920.9 linkuse as main transcript	c.46C>T	p.Leu16=	synonymous_variant	2/22	1	NM_182977.3	P1

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

95790

AN:

151908

Hom.:

32630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.639

GnomAD3 exomes

AF:

0.519

AC:

130408

AN:

251364

Hom.:

37212

AF XY:

0.522

AC XY:

70931

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.899

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.554

AC:

809760

AN:

1461144

Hom.:

230728

Cov.:

AF XY:

0.553

AC XY:

402249

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.902

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.510

Gnomad4 FIN exome

AF:

0.509

Gnomad4 NFE exome

AF:

0.566

Gnomad4 OTH exome

AF:

0.572

GnomAD4 genome

AF:

0.631

AC:

95890

AN:

152024

Hom.:

32681

Cov.:

AF XY:

0.621

AC XY:

46104

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.887

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.611

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.586

Hom.:

33916

Bravo

AF:

0.640

Asia WGS

AF:

0.417

AC:

1453

AN:

3478

EpiCase

AF:

0.581

EpiControl

AF:

0.589

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Glucocorticoid deficiency 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.1

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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