rs769355226

Variant names:

• chr11-62671762-A-C
• NM_024099.5:c.-209T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-62671762-A-C
• chr11-62671762-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024099.5(LBHD1):​c.-209T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LBHD1 NM_024099.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

Genes affected

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

UQCC3 (HGNC:34399): (ubiquinol-cytochrome c reductase complex assembly factor 3) Complex III is a mitochondrial inner membrane protein complex that transfers electrons from ubiquinol to cytochrome c. This gene encodes a protein that functions in complex III assembly. Mutations in this gene result in Mitochondrial complex III deficiency, nuclear type 9. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1790412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBHD1	NM_024099.5	c.-209T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000354588.8	NP_077004.2
UQCC3	NM_001085372.3	c.17A>C	p.Lys6Thr	missense_variant	Exon 1 of 2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5	c.-209T>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBHD1	ENST00000354588.8	c.-209T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_024099.5	ENSP00000346600.3
UQCC3	ENST00000377953.4	c.17A>C	p.Lys6Thr	missense_variant	Exon 1 of 2	1	NM_001085372.3	ENSP00000367189.3
LBHD1	ENST00000354588.8	c.-209T>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_024099.5	ENSP00000346600.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727060

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.0074	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.14
Sift	Benign	0.26	T;T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.99	D;D
Vest4		0.36
MutPred		0.31		Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);
MVP		0.12
MPC		0.91
ClinPred		0.75	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.41

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: chr11-62439234;