X-47142363-G-A

Position:

• chrX-47142363-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001135998.3(NDUFB11):​c.416C>T​(p.Ser139Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,801 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: NDUFB11 NM_001135998.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.47

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4078675).
• BP6: Variant X-47142363-G-A is Benign according to our data. Variant chrX-47142363-G-A is described in ClinVar as [Benign]. Clinvar id is 1685961.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB11	NM_001135998.3	c.416C>T	p.Ser139Phe	missense_variant	3/3	ENST00000377811.4	NP_001129470.1
NDUFB11	NM_019056.7	c.446C>T	p.Ser149Phe	missense_variant	3/3		NP_061929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4	c.416C>T	p.Ser139Phe	missense_variant	3/3	1	NM_001135998.3	ENSP00000367042	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097801 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363181

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.51	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.34
MutPred		0.51		Loss of disorder (P = 0.0087);.;
MVP		0.53
MPC		1.1
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.85
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47001762;