Genetic Variant NNT:p.Gly11Ser (chr5-43609226-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182977.3(NNT):c.31G>A(p.Gly11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G11V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NNT
NM_182977.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.89

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

glucocorticoid deficiency 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
familial glucocorticoid deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NNT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15194714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182977.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NNT	NM_182977.3	MANE Select	c.31G>A	p.Gly11Ser	missense	Exon 2 of 22	NP_892022.2	Q13423
NNT	NM_012343.4		c.31G>A	p.Gly11Ser	missense	Exon 2 of 22	NP_036475.3
NNT	NM_001331026.2		c.-133G>A		5_prime_UTR	Exon 2 of 21	NP_001317955.1	E9PCX7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NNT	ENST00000344920.9	TSL:1 MANE Select	c.31G>A	p.Gly11Ser	missense	Exon 2 of 22	ENSP00000343873.4	Q13423
NNT	ENST00000264663.9	TSL:1	c.31G>A	p.Gly11Ser	missense	Exon 2 of 22	ENSP00000264663.5	Q13423
NNT	ENST00000653251.1		c.31G>A	p.Gly11Ser	missense	Exon 3 of 23	ENSP00000499281.1	Q13423

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111892

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.15

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

-0.34

PhyloP100

2.9

PrimateAI

Benign

0.36

PROVEAN

Benign

0.070

REVEL

Uncertain

0.29

Sift

Benign

0.49

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.25

MutPred

0.43

Gain of sheet (P = 0.0344)

MVP

0.47

MPC

0.26

ClinPred

0.39

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.049

gMVP

0.43

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over