X-47142592-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001135998.3(NDUFB11):c.338+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,209,141 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 113 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 8 hem., cov: 23)
  • Exomes 𝑓: 0.00022 (0 hom. 105 hem.)
• Consequence: NDUFB11 NM_001135998.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0730

Genes affected

NDUFB11 (HGNC:20372): (NADH:ubiquinone oxidoreductase subunit B11) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to ubiquinone. Mutations in the human gene are associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant X-47142592-C-T is Benign according to our data. Variant chrX-47142592-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 704717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFB11	NM_001135998.3	c.338+22G>A		intron_variant		ENST00000377811.4
NDUFB11	NM_019056.7	c.360G>A	p.Ala120=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFB11	ENST00000377811.4	c.338+22G>A		intron_variant		1	NM_001135998.3	P1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 111983 Hom.: 0 Cov.: 23 AF XY: 0.000234 AC XY: 8 AN XY: 34143

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.000327

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000342 AC: 62 AN: 181189 Hom.: 0 AF XY: 0.000395 AC XY: 26 AN XY: 65843

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.000503

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000219 AC: 240 AN: 1097105 Hom.: 0 Cov.: 31 AF XY: 0.000290 AC XY: 105 AN XY: 362539

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.000296

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000326

GnomAD4 genome AF: 0.000125 AC: 14 AN: 112036 Hom.: 0 Cov.: 23 AF XY: 0.000234 AC XY: 8 AN XY: 34206

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00111

Gnomad4 FIN AF: 0.000327

Gnomad4 NFE AF: 0.000169

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000132

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 26, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	NDUFB11: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	7.2
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs191275787; hg19: chrX-47001991; COSMIC: COSV52102318; COSMIC: COSV52102318;