X-47142690-G-C

Variant names:

• chrX-47142690-G-C
• rs786205225
• NM_001135998.3:c.262C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001135998.3(NDUFB11):​c.262C>G​(p.Arg88Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,987 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: NDUFB11 NM_001135998.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135998.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB11	NM_001135998.3	MANE Select	c.262C>G	p.Arg88Gly	missense	Exon 2 of 3	NP_001129470.1	Q9NX14-1
	NDUFB11	NM_019056.7		c.262C>G	p.Arg88Gly	missense	Exon 2 of 3	NP_061929.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB11	ENST00000377811.4	TSL:1 MANE Select	c.262C>G	p.Arg88Gly	missense	Exon 2 of 3	ENSP00000367042.3	Q9NX14-1
	NDUFB11	ENST00000276062.9	TSL:1	c.255C>G	p.Cys85Trp	missense	Exon 2 of 3	ENSP00000276062.9	A0A8J8YU24
	NDUFB11	ENST00000687244.1		c.262C>G	p.Arg88Gly	missense	Exon 2 of 3	ENSP00000509334.1	Q9NX14-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097987 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363347

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841922

Other (OTH) AF: 0.00 AC: 0 AN: 46088

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.87
MutPred		0.45		Gain of sheet (P = 0.039)
MVP		0.85
MPC		1.3
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.93
gMVP		0.59
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs786205225; hg19: chrX-47002089;