dbSNP rs143509965: UQCC3:p.Trp76Gly (chr11-62672058-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001085372.3(UQCC3):c.226T>G(p.Trp76Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,609,326 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 11 hom. )

Consequence

UQCC3
NM_001085372.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.611

Publications

4 publications found

Variant links:

Genes affected

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]

UQCC3 links:

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]

LBHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008778036).

BP6

Variant 11-62672058-T-G is Benign according to our data. Variant chr11-62672058-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376907.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 = 0.00716 (1090/152302) while in subpopulation AFR AF = 0.0254 (1056/41570). AF 95% confidence interval is 0.0241. There are 13 homozygotes in GnomAd4. There are 527 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085372.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCC3	NM_001085372.3	MANE Select	c.226T>G	p.Trp76Gly	missense	Exon 2 of 2	NP_001078841.1	Q6UW78
LBHD1	NM_024099.5	MANE Select	c.-505A>C		5_prime_UTR	Exon 1 of 7	NP_077004.2
LBHD1	NM_001394599.1		c.-311A>C		5_prime_UTR	Exon 1 of 7	NP_001381528.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UQCC3	ENST00000377953.4	TSL:1 MANE Select	c.226T>G	p.Trp76Gly	missense	Exon 2 of 2	ENSP00000367189.3	Q6UW78
LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.-505A>C		5_prime_UTR	Exon 1 of 7	ENSP00000346600.3	Q9BQE6-2
UQCC3	ENST00000531323.1	TSL:3	c.226T>G	p.Trp76Gly	missense	Exon 3 of 3	ENSP00000432692.1	Q6UW78

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1088

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00162

AC:

381

AN:

234640

AF XY:

0.00118

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000567

Gnomad OTH exome

AF:

0.000869

GnomAD4 exome

AF:

0.000738

AC:

1075

AN:

1457024

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

406

AN XY:

724416

show subpopulations

African (AFR)

AF:

0.0273

AC:

911

AN:

33428

American (AMR)

AF:

0.000801

AC:

AN:

43674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25938

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000468

AC:

AN:

85508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52844

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1110158

Other (OTH)

AF:

0.00145

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00716

AC:

1090

AN:

152302

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0254

AC:

1056

AN:

41570

American (AMR)

AF:

0.00124

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68030

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00786

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0219

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00197

AC:

239

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Uncertain

0.65

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.95

PhyloP100

0.61

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.083

Sift

Benign

0.11

Sift4G

Uncertain

0.051

Polyphen

0.84

Vest4

0.49

MVP

0.19

MPC

1.1

ClinPred

0.055

GERP RS

0.086

PromoterAI

0.028

Neutral

(source)

Varity_R

0.28

gMVP

0.094

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over