rs1246105623

Variant names:

• chrX-47142334-G-A
• rs1246105623
• NM_001135998.3:c.445C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-47142334-G-A
• chrX-47142334-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001135998.3(NDUFB11):​c.445C>T​(p.Leu149Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,608 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: NDUFB11 NM_001135998.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=2.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB11	NM_001135998.3	c.445C>T	p.Leu149Leu	synonymous_variant	Exon 3 of 3	ENST00000377811.4	NP_001129470.1
NDUFB11	NM_019056.7	c.475C>T	p.Leu159Leu	synonymous_variant	Exon 3 of 3		NP_061929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB11	ENST00000377811.4	c.445C>T	p.Leu149Leu	synonymous_variant	Exon 3 of 3	1	NM_001135998.3	ENSP00000367042.3

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111733 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33897

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000954

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095875 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1 AN XY: 361491

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: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111733 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33897

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000954

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs1246105623; hg19: chrX-47001733;