rs374083393

Variant names:

• chrX-47142352-C-G
• rs374083393
• NM_001135998.3:c.427G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-47142352-C-G
• chrX-47142352-C-T

Variant summary

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

The NM_001135998.3(NDUFB11):​c.427G>C​(p.Asp143His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D143N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: NDUFB11 NM_001135998.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• 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, 0.809

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.427G>C	p.Asp143His	missense	Exon 3 of 3	NP_001129470.1	Q9NX14-1
	NDUFB11	NM_019056.7		c.457G>C	p.Asp153His	missense	Exon 3 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.427G>C	p.Asp143His	missense	Exon 3 of 3	ENSP00000367042.3	Q9NX14-1
	NDUFB11	ENST00000276062.9	TSL:1	c.*84G>C		3_prime_UTR	Exon 3 of 3	ENSP00000276062.9	A0A8J8YU24
	NDUFB11	ENST00000687244.1		c.457G>C	p.Asp153His	missense	Exon 3 of 3	ENSP00000509334.1	Q9NX14-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000555 AC: 1 AN: 180153 AF XY: 0.00

Gnomad AFR exome AF: 0.0000771

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	NDUFB11-related disorders (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.68		Loss of disorder (P = 0.064)
MVP		0.86
MPC		1.2
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.96
gMVP		0.78
Mutation Taster		=70/30	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: rs374083393; hg19: chrX-47001751;