NM_006003.3:c.24A>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006003.3(UQCRFS1):​c.24A>C​(p.Ser8Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,118 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. Synonymous variant affecting the same amino acid position (i.e. S8S) has been classified as Benign.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 37)
Exomes š‘“: 0.0000066 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

UQCRFS1
NM_006003.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.645
Variant links:
Genes affected
UQCRFS1 (HGNC:12587): (ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1) Predicted to enable oxidoreductase activity. Involved in mitochondrial respiratory chain complex III assembly and respiratory electron transport chain. Located in mitochondrion. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. Implicated in mitochondrial complex III deficiency. [provided by Alliance of Genome Resources, Apr 2022]
UQCRFS1-DT (HGNC:55295): (UQCRFS1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=-0.59).
BP7
Synonymous conserved (PhyloP=-0.645 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UQCRFS1NM_006003.3 linkc.24A>C p.Ser8Ser synonymous_variant Exon 1 of 2 ENST00000304863.6 NP_005994.2 P47985
UQCRFS1-DTNR_184021.1 linkn.-158T>G upstream_gene_variant
UQCRFS1-DTNR_184022.1 linkn.-158T>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UQCRFS1ENST00000304863.6 linkc.24A>C p.Ser8Ser synonymous_variant Exon 1 of 2 1 NM_006003.3 ENSP00000306397.3 P47985
UQCRFS1-DTENST00000587859.1 linkn.-140T>G upstream_gene_variant 2
UQCRFS1-DTENST00000590607.2 linkn.-188T>G upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152008
Hom.:
0
Cov.:
37
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000977
AC:
1
AN:
102368
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
57472
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000481
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000663
AC:
9
AN:
1357846
Hom.:
0
Cov.:
51
AF XY:
0.00000746
AC XY:
5
AN XY:
670032
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000315
Gnomad4 SAS exome
AF:
0.0000515
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.36e-7
Gnomad4 OTH exome
AF:
0.0000529
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
37
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
8.5
DANN
Benign
0.45

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11666764; hg19: chr19-29704002; API