X-47142424-G-T

Variant names:

• chrX-47142424-G-T
• rs1253291602
• NM_001135998.3:c.355C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135998.3(NDUFB11):​c.355C>A​(p.Arg119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R119C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: NDUFB11 NM_001135998.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3	c.355C>A	p.Arg119Ser	missense_variant	Exon 3 of 3	ENST00000377811.4	NP_001129470.1
NDUFB11	NM_019056.7	c.385C>A	p.Arg129Ser	missense_variant	Exon 3 of 3		NP_061929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4	c.355C>A	p.Arg119Ser	missense_variant	Exon 3 of 3	1	NM_001135998.3	ENSP00000367042.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.0	M;.
PhyloP100		1.8
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.97	D;D
Vest4		0.53
MutPred		0.58		Gain of phosphorylation at R119 (P = 0.0148);.;
MVP		0.74
MPC		1.2
ClinPred		0.99	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.88
gMVP		0.85
Mutation Taster		=72/28	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: rs1253291602; hg19: chrX-47001823; COSMIC: COSV99333235; COSMIC: COSV99333235;