X-47144528-G-A

Variant names:

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

RBM10 (HGNC:9896): (RNA binding motif protein 10) This gene encodes a nuclear protein that belongs to a family proteins that contain an RNA-binding motif. The encoded protein associates with hnRNP proteins and may be involved in regulating alternative splicing. Defects in this gene are the cause of the X-linked recessive disorder, TARP syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

RBM10 Gene-Disease associations (from GenCC):

• TARP syndrome

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

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).

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.152C>T	p.Pro51Leu	missense	Exon 1 of 3	NP_001129470.1	Q9NX14-1
	NDUFB11	NM_019056.7		c.152C>T	p.Pro51Leu	missense	Exon 1 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.152C>T	p.Pro51Leu	missense	Exon 1 of 3	ENSP00000367042.3	Q9NX14-1
	NDUFB11	ENST00000276062.9	TSL:1	c.152C>T	p.Pro51Leu	missense	Exon 1 of 3	ENSP00000276062.9	A0A8J8YU24
	NDUFB11	ENST00000687244.1		c.152C>T	p.Pro51Leu	missense	Exon 1 of 3	ENSP00000509334.1	Q9NX14-2

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 v4.9

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
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.17
Sift	Benign	0.17	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.30	B
Vest4		0.15
MutPred		0.50		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;