rs150506634

Variant names:

• chrX-47144528-G-A
• rs150506634
• NM_001135998.3:c.152C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-47144528-G-A
• chrX-47144528-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135998.3(NDUFB11):​c.152C>T​(p.Pro51Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000966 in 1,034,871 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. P51Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.7e-7 (0 hom. 0 hem.)
• Consequence: NDUFB11 NM_001135998.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1553323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3	c.152C>T	p.Pro51Leu	missense_variant	Exon 1 of 3	ENST00000377811.4	NP_001129470.1
NDUFB11	NM_019056.7	c.152C>T	p.Pro51Leu	missense_variant	Exon 1 of 3		NP_061929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4	c.152C>T	p.Pro51Leu	missense_variant	Exon 1 of 3	1	NM_001135998.3	ENSP00000367042.3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.66e-7 AC: 1 AN: 1034871 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 325893

African (AFR) AF: 0.00 AC: 0 AN: 24741

American (AMR) AF: 0.00 AC: 0 AN: 30482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17808

East Asian (EAS) AF: 0.00 AC: 0 AN: 27707

South Asian (SAS) AF: 0.00 AC: 0 AN: 47810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37845

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2905

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 802943

Other (OTH) AF: 0.00 AC: 0 AN: 42630

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T;.
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		4.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.17
Sift	Benign	0.17	T;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.30	B;B
Vest4		0.15
MutPred		0.50		Loss of glycosylation at P51 (P = 0.012);Loss of glycosylation at P51 (P = 0.012);
MVP		0.33
MPC		0.59
ClinPred		0.59	D
GERP RS		4.1
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.25
Mutation Taster		=91/9	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: rs150506634; hg19: chrX-47003927;