X-47142592-C-T

Variant names:

• chrX-47142592-C-T
• rs191275787
• NM_001135998.3:c.338+22G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

NDUFB11 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• linear skin defects with multiple congenital anomalies 3

  Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial complex I deficiency, nuclear type 30

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• linear skin defects with multiple congenital anomalies

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3	c.338+22G>A		intron_variant	Intron 2 of 2	ENST00000377811.4	NP_001129470.1
NDUFB11	NM_019056.7	c.360G>A	p.Ala120Ala	synonymous_variant	Exon 2 of 3		NP_061929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4	c.338+22G>A		intron_variant	Intron 2 of 2	1	NM_001135998.3	ENSP00000367042.3

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 111983 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.000342 AC: 62 AN: 181189 AF XY: 0.000395

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 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

African (AFR) AF: 0.000114 AC: 3 AN: 26379

American (AMR) AF: 0.00 AC: 0 AN: 35070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19270

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30200

South Asian (SAS) AF: 0.00165 AC: 89 AN: 53905

European-Finnish (FIN) AF: 0.000296 AC: 12 AN: 40494

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4127

European-Non Finnish (NFE) AF: 0.000140 AC: 118 AN: 841610

Other (OTH) AF: 0.000326 AC: 15 AN: 46050

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

African (AFR) AF: 0.00 AC: 0 AN: 30837

American (AMR) AF: 0.00 AC: 0 AN: 10519

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00111 AC: 3 AN: 2707

European-Finnish (FIN) AF: 0.000327 AC: 2 AN: 6108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53203

Other (OTH) AF: 0.00 AC: 0 AN: 1528

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

Sep 08, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NDUFB11: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.52
PhyloP100		-0.073
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs191275787; hg19: chrX-47001991; COSMIC: COSV52102318; COSMIC: COSV52102318;