NM_182977.3:c.152-26_152-25insA

Variant names:

• chr5-43612882-T-TA
• rs139409541
• NM_182977.3:c.152-26_152-25insA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_182977.3(NNT):​c.152-26_152-25insA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (18505 hom., cov: 0)
  • Exomes 𝑓: 0.46 (131295 hom.)
• Consequence: NNT NM_182977.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.110
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-43612882-T-TA is Benign according to our data. Variant chr5-43612882-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1325908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNT	NM_182977.3	MANE Select	c.152-26_152-25insA		intron	N/A	NP_892022.2	Q13423
	NNT	NM_012343.4		c.152-26_152-25insA		intron	N/A	NP_036475.3
	NNT	NM_001331026.2		c.-12-2966_-12-2965insA		intron	N/A	NP_001317955.1	E9PCX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNT	ENST00000344920.9	TSL:1 MANE Select	c.152-26_152-25insA		intron	N/A	ENSP00000343873.4	Q13423
	NNT	ENST00000264663.9	TSL:1	c.152-26_152-25insA		intron	N/A	ENSP00000264663.5	Q13423
	NNT	ENST00000653251.1		c.152-26_152-25insA		intron	N/A	ENSP00000499281.1	Q13423

Frequencies

GnomAD3 genomes AF: 0.502 AC: 73155 AN: 145674 Hom.: 18511 Cov.: 0

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.537

GnomAD2 exomes AF: 0.447 AC: 93016 AN: 208318 AF XY: 0.452

Gnomad AFR exome AF: 0.587

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.113

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.507

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.463 AC: 560001 AN: 1208838 Hom.: 131295 Cov.: 19 AF XY: 0.462 AC XY: 280752 AN XY: 607484

African (AFR) AF: 0.591 AC: 15982 AN: 27064

American (AMR) AF: 0.310 AC: 11218 AN: 36164

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 12140 AN: 23108

East Asian (EAS) AF: 0.120 AC: 4438 AN: 36886

South Asian (SAS) AF: 0.375 AC: 27821 AN: 74268

European-Finnish (FIN) AF: 0.443 AC: 22849 AN: 51530

Middle Eastern (MID) AF: 0.581 AC: 3021 AN: 5196

European-Non Finnish (NFE) AF: 0.485 AC: 438176 AN: 903064

Other (OTH) AF: 0.472 AC: 24356 AN: 51558

GnomAD4 genome AF: 0.502 AC: 73169 AN: 145780 Hom.: 18505 Cov.: 0 AF XY: 0.494 AC XY: 35092 AN XY: 71062

African (AFR) AF: 0.580 AC: 23793 AN: 41042

American (AMR) AF: 0.423 AC: 6208 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1727 AN: 3336

East Asian (EAS) AF: 0.113 AC: 457 AN: 4052

South Asian (SAS) AF: 0.382 AC: 1687 AN: 4414

European-Finnish (FIN) AF: 0.450 AC: 4519 AN: 10036

Middle Eastern (MID) AF: 0.667 AC: 184 AN: 276

European-Non Finnish (NFE) AF: 0.508 AC: 33069 AN: 65084

Other (OTH) AF: 0.535 AC: 1073 AN: 2006

Alfa AF: 0.456 Hom.: 1592

Asia WGS AF: 0.262 AC: 864 AN: 3284

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Glucocorticoid deficiency 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
Mutation Taster		=25/75	disease causing

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

Other links and lift over

dbSNP: rs139409541; hg19: chr5-43612984;