chr2-201079273-C-T

Position:

• chr2-201079273-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002491.3(NDUFB3):​c.140+251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 151,828 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (18 hom., cov: 32)
• Consequence: NDUFB3 NM_002491.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 2-201079273-C-T is Benign according to our data. Variant chr2-201079273-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 672606.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1729/151828) while in subpopulation NFE AF= 0.0167 (1135/67922). AF 95% confidence interval is 0.0159. There are 18 homozygotes in gnomad4. There are 828 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB3	NM_002491.3	c.140+251C>T		intron_variant		ENST00000237889.9	NP_002482.1
NDUFB3	NM_001257102.2	c.140+251C>T		intron_variant			NP_001244031.1
NDUFB3	XM_011511230.4	c.140+251C>T		intron_variant			XP_011509532.1
NDUFB3	XM_047444488.1	c.140+251C>T		intron_variant			XP_047300444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB3	ENST00000237889.9	c.140+251C>T		intron_variant		1	NM_002491.3	ENSP00000237889	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1728 AN: 151712 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00322

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.00637

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0121

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0114 AC: 1729 AN: 151828 Hom.: 18 Cov.: 32 AF XY: 0.0112 AC XY: 828 AN XY: 74176

Gnomad4 AFR AF: 0.00321

Gnomad4 AMR AF: 0.00636

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0121

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0124

Alfa AF: 0.0158 Hom.: 1

Bravo AF: 0.0101

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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	-1.0
CADD	Benign	0.92
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs144629284; hg19: chr2-201943996;