11-62671942-C-T

Position:

• chr11-62671942-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000377953.4(UQCC3):​c.121-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,613,812 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (29 hom.)
• Consequence: UQCC3 ENST00000377953.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001455
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.659

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-62671942-C-T is Benign according to our data. Variant chr11-62671942-C-T is described in ClinVar as [Benign]. Clinvar id is 381444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00991 (1509/152330) while in subpopulation AFR AF= 0.0347 (1443/41572). AF 95% confidence interval is 0.0332. There are 27 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBHD1	NM_024099.5	c.-389G>A		5_prime_UTR_variant	1/7	ENST00000354588.8	NP_077004.2
UQCC3	NM_001085372.3	c.121-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377953.4	NP_001078841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBHD1	ENST00000354588.8	c.-389G>A		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600	P1
UQCC3	ENST00000377953.4	c.121-11C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001085372.3	ENSP00000367189	P1
LBHD1	ENST00000528862.2	c.93+185G>A		intron_variant		3		ENSP00000434489
UQCC3	ENST00000531323.1	c.121-11C>T		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000432692	P1

Frequencies

GnomAD3 genomes AF: 0.00986 AC: 1501 AN: 152212 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00235 AC: 582 AN: 247738 Hom.: 6 AF XY: 0.00173 AC XY: 233 AN XY: 134760

Gnomad AFR exome AF: 0.0348

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000961 AC: 1404 AN: 1461482 Hom.: 29 Cov.: 31 AF XY: 0.000792 AC XY: 576 AN XY: 727022

Gnomad4 AFR exome AF: 0.0370

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00991 AC: 1509 AN: 152330 Hom.: 27 Cov.: 32 AF XY: 0.00960 AC XY: 715 AN XY: 74494

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00481 Hom.: 1

Bravo AF: 0.0108

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 17, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.6
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.16		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: rs184836500; hg19: chr11-62439414;