Variant chr2-201085443-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1

The NM_002491.3(NDUFB3):c.141-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,119,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 31)

Exomes 𝑓: 0.017 ( 0 hom. )

Consequence

NDUFB3
NM_002491.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.306

Variant links:

Genes affected

NDUFB3 (HGNC:7698): (NADH:ubiquinone oxidoreductase subunit B3) This gene encodes an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which is the first enzyme in the electron transport chain of mitochondria. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. Mutations in this gene contribute to mitochondrial complex 1 deficiency. Alternative splicing results in multiple transcript variants encoding the same protein. Humans have multiple pseudogenes of this gene. [provided by RefSeq, Mar 2012]

NDUFB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 2-201085443-CT-C is Benign according to our data. Variant chr2-201085443-CT-C is described in ClinVar as [Benign]. Clinvar id is 516886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-201085443-CT-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0171 (16593/972614) while in subpopulation AMR AF= 0.0331 (817/24652). AF 95% confidence interval is 0.0313. There are 0 homozygotes in gnomad4_exome. There are 8683 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NDUFB3	NM_002491.3 linkuse as main transcript	c.141-5del	splice_polypyrimidine_tract_variant, intron_variant	ENST00000237889.9	NP_002482.1
NDUFB3	NM_001257102.2 linkuse as main transcript	c.141-5del	splice_polypyrimidine_tract_variant, intron_variant		NP_001244031.1
NDUFB3	XM_011511230.4 linkuse as main transcript	c.141-5del	splice_polypyrimidine_tract_variant, intron_variant		XP_011509532.1
NDUFB3	XM_047444488.1 linkuse as main transcript	c.141-5del	splice_polypyrimidine_tract_variant, intron_variant		XP_047300444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB3	ENST00000237889.9 linkuse as main transcript	c.141-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002491.3	ENSP00000237889	P1

Frequencies

GnomAD3 genomes

AF:

0.000307

AC:

AN:

146524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000426

Gnomad FIN

AF:

0.00152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000166

Gnomad OTH

AF:

0.000500

GnomAD3 exomes

AF:

0.0567

AC:

4813

AN:

84856

Hom.:

AF XY:

0.0588

AC XY:

2685

AN XY:

45690

show subpopulations

Gnomad AFR exome

AF:

0.0370

Gnomad AMR exome

AF:

0.0787

Gnomad ASJ exome

AF:

0.0467

Gnomad EAS exome

AF:

0.0502

Gnomad SAS exome

AF:

0.0577

Gnomad FIN exome

AF:

0.0558

Gnomad NFE exome

AF:

0.0569

Gnomad OTH exome

AF:

0.0538

GnomAD4 exome

AF:

0.0171

AC:

16593

AN:

972614

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

8683

AN XY:

483054

show subpopulations

Gnomad4 AFR exome

AF:

0.0186

Gnomad4 AMR exome

AF:

0.0331

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0183

Gnomad4 SAS exome

AF:

0.0287

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.000321

AC:

AN:

146596

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

AN XY:

71328

show subpopulations

Gnomad4 AFR

AF:

0.000348

Gnomad4 AMR

AF:

0.000274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000640

Gnomad4 FIN

AF:

0.00152

Gnomad4 NFE

AF:

0.000166

Gnomad4 OTH

AF:

0.000495

Alfa

AF:

0.0252

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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