5-43609275-G-A

Position:

chr5-43609275-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182977.3(NNT):c.80G>A(p.Arg27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000944 in 1,613,974 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 10 hom. )

Consequence

NNT
NM_182977.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.902

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039408505).

BP6

Variant 5-43609275-G-A is Benign according to our data. Variant chr5-43609275-G-A is described in ClinVar as [Benign]. Clinvar id is 703892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00478 (728/152254) while in subpopulation AFR AF= 0.0157 (654/41548). AF 95% confidence interval is 0.0147. There are 5 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NNT	NM_182977.3 linkuse as main transcript	c.80G>A	p.Arg27His	missense_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.80G>A	p.Arg27His	missense_variant	2/22	1	NM_182977.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00475

AC:

723

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

251452

Hom.:

AF XY:

0.000883

AC XY:

120

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000545

AC:

796

AN:

1461720

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

330

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00478

AC:

728

AN:

152254

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

354

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000713

Hom.:

Bravo

AF:

0.00580

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	Jan 08, 2024	- -

Glucocorticoid deficiency 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Nov 08, 2018

This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.011

.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.63

T;T;.;T

MetaRNN

Benign

0.0039

T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

-0.34

.;.;N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.050

N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.37

T;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0

.;.;B;B

Vest4

0.054, 0.052

MVP

0.65

MPC

0.32

ClinPred

0.0013

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.32

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