X-47142212-C-T

Variant names:

• chrX-47142212-C-T
• rs73630256
• ENST00000687244.1:c.*105G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000687244.1(NDUFB11):​c.*105G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,065,501 control chromosomes in the GnomAD database, including 259 homozygotes. There are 1,653 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (154 hom., 854 hem., cov: 22)
  • Exomes 𝑓: 0.0033 (105 hom. 799 hem.)
• Consequence: NDUFB11 ENST00000687244.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.145
• Publications: 1 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-47142212-C-T is Benign according to our data. Variant chrX-47142212-C-T is described in ClinVar as [Benign]. Clinvar id is 1284247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3	c.*105G>A		downstream_gene_variant		ENST00000377811.4	NP_001129470.1
NDUFB11	NM_019056.7	c.*105G>A		downstream_gene_variant			NP_061929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4	c.*105G>A		downstream_gene_variant		1	NM_001135998.3	ENSP00000367042.3

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 3388 AN: 111687 Hom.: 152 Cov.: 22

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00840

Gnomad NFE AF: 0.000564

Gnomad OTH AF: 0.0267

GnomAD4 exome AF: 0.00329 AC: 3138 AN: 953761 Hom.: 105 Cov.: 17 AF XY: 0.00285 AC XY: 799 AN XY: 280667

African (AFR) AF: 0.108 AC: 2489 AN: 23105

American (AMR) AF: 0.00649 AC: 162 AN: 24971

Ashkenazi Jewish (ASJ) AF: 0.0000621 AC: 1 AN: 16096

East Asian (EAS) AF: 0.00 AC: 0 AN: 26716

South Asian (SAS) AF: 0.000254 AC: 11 AN: 43270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26022

Middle Eastern (MID) AF: 0.00652 AC: 17 AN: 2606

European-Non Finnish (NFE) AF: 0.000165 AC: 124 AN: 749914

Other (OTH) AF: 0.00813 AC: 334 AN: 41061

GnomAD4 genome AF: 0.0304 AC: 3394 AN: 111740 Hom.: 154 Cov.: 22 AF XY: 0.0252 AC XY: 854 AN XY: 33932

African (AFR) AF: 0.105 AC: 3211 AN: 30679

American (AMR) AF: 0.0105 AC: 111 AN: 10532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6030

Middle Eastern (MID) AF: 0.00922 AC: 2 AN: 217

European-Non Finnish (NFE) AF: 0.000564 AC: 30 AN: 53176

Other (OTH) AF: 0.0263 AC: 40 AN: 1519

Alfa AF: 0.0172 Hom.: 73

Bravo AF: 0.0348

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.44
PhyloP100		-0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73630256; hg19: chrX-47001611;