2-201072375-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002491.3(NDUFB3):​c.-3+316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00088 in 152,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NDUFB3
NM_002491.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0260
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 2-201072375-A-G is Benign according to our data. Variant chr2-201072375-A-G is described in ClinVar as [Benign]. Clinvar id is 378250.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDUFB3NM_002491.3 linkc.-3+316A>G intron_variant Intron 1 of 2 ENST00000237889.9 NP_002482.1 O43676A0A024R413
NDUFB3XM_047444488.1 linkc.-781A>G 5_prime_UTR_variant Exon 2 of 4 XP_047300444.1
NDUFB3NM_001257102.2 linkc.-3+14A>G intron_variant Intron 2 of 3 NP_001244031.1 O43676A0A024R413
NDUFB3XM_011511230.4 linkc.-3+14A>G intron_variant Intron 2 of 3 XP_011509532.1 O43676A0A024R413

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDUFB3ENST00000237889.9 linkc.-3+316A>G intron_variant Intron 1 of 2 1 NM_002491.3 ENSP00000237889.4 O43676

Frequencies

GnomAD3 genomes
AF:
0.000874
AC:
133
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0126
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000764
Gnomad OTH
AF:
0.00191
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000880
AC:
134
AN:
152326
Hom.:
0
Cov.:
32
AF XY:
0.00111
AC XY:
83
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0128
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000764
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000106
Hom.:
0
Bravo
AF:
0.000555
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 17, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
7.4
DANN
Benign
0.73

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.

Other links and lift over

dbSNP: rs539378055; hg19: chr2-201937098; API