Genetic Variant NM_006003.3:c.24A>C (chr19-29213095-T-G) – ACMG Classification: Likely_benign (-3 pts)

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: 𝑓 0.000020 ( 0 hom., cov: 37)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UQCRFS1
NM_006003.3 synonymous

Scores

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 links:

UQCRFS1-DT (HGNC:55295): (UQCRFS1 divergent transcript)

UQCRFS1-DT links:

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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
UQCRFS1	NM_006003.3 link	c.24A>C	p.Ser8Ser	synonymous_variant	Exon 1 of 2	ENST00000304863.6	NP_005994.2	P47985
UQCRFS1-DT	NR_184021.1 link	n.-158T>G		upstream_gene_variant
UQCRFS1-DT	NR_184022.1 link	n.-158T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UQCRFS1	ENST00000304863.6 link	c.24A>C	p.Ser8Ser	synonymous_variant	Exon 1 of 2	1	NM_006003.3	ENSP00000306397.3	P47985
UQCRFS1-DT	ENST00000587859.1 link	n.-140T>G		upstream_gene_variant		2
UQCRFS1-DT	ENST00000590607.2 link	n.-188T>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152008

Hom.:

Cov.:

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:

AN:

102368

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1357846

Hom.:

Cov.:

AF XY:

0.00000746

AC XY:

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:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over