19-29213095-T-C

Variant names:

• chr19-29213095-T-C
• rs11666764
• NM_006003.3:c.24A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006003.3(UQCRFS1):​c.24A>G​(p.Ser8Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,110 control chromosomes in the GnomAD database, including 65,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65752 hom., cov: 37)
  • Exomes 𝑓: 0.92 (579285 hom.)
  • Failed GnomAD Quality Control
• Consequence: UQCRFS1 NM_006003.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.645

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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 19-29213095-T-C is Benign according to our data. Variant chr19-29213095-T-C is described in ClinVar as [Benign]. Clinvar id is 1684191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRFS1	NM_006003.3	c.24A>G	p.Ser8Ser	synonymous_variant	Exon 1 of 2	ENST00000304863.6	NP_005994.2
UQCRFS1-DT	NR_184021.1	n.-158T>C		upstream_gene_variant
UQCRFS1-DT	NR_184022.1	n.-158T>C		upstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141304 AN: 152000 Hom.: 65700 Cov.: 37

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.922

GnomAD2 exomes AF: 0.932 AC: 95447 AN: 102368 AF XY: 0.933

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.945

Gnomad ASJ exome AF: 0.907

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.936

Gnomad NFE exome AF: 0.910

Gnomad OTH exome AF: 0.913

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.924 AC: 1252892 AN: 1355800 Hom.: 579285 Cov.: 51 AF XY: 0.925 AC XY: 618591 AN XY: 669030

Gnomad4 AFR exome AF: 0.935 AC: 26050 AN: 27854

Gnomad4 AMR exome AF: 0.942 AC: 31182 AN: 33090

Gnomad4 ASJ exome AF: 0.910 AC: 21910 AN: 24066

Gnomad4 EAS exome AF: 1.00 AC: 31755 AN: 31764

Gnomad4 SAS exome AF: 0.955 AC: 74150 AN: 77648

Gnomad4 FIN exome AF: 0.931 AC: 30918 AN: 33202

Gnomad4 NFE exome AF: 0.919 AC: 980441 AN: 1066974

Gnomad4 Remaining exome AF: 0.925 AC: 52347 AN: 56588

GnomAD4 genome AF: 0.930 AC: 141411 AN: 152110 Hom.: 65752 Cov.: 37 AF XY: 0.931 AC XY: 69251 AN XY: 74354

Gnomad4 AFR AF: 0.935 AC: 0.934574 AN: 0.934574

Gnomad4 AMR AF: 0.929 AC: 0.928674 AN: 0.928674

Gnomad4 ASJ AF: 0.910 AC: 0.909562 AN: 0.909562

Gnomad4 EAS AF: 0.999 AC: 0.99903 AN: 0.99903

Gnomad4 SAS AF: 0.966 AC: 0.966487 AN: 0.966487

Gnomad4 FIN AF: 0.939 AC: 0.938939 AN: 0.938939

Gnomad4 NFE AF: 0.919 AC: 0.919297 AN: 0.919297

Gnomad4 OTH AF: 0.924 AC: 0.924171 AN: 0.924171

Alfa AF: 0.913 Hom.: 5897

Bravo AF: 0.928

Asia WGS AF: 0.981 AC: 3413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mitochondrial complex 3 deficiency, nuclear type 10 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.8
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11666764; hg19: chr19-29704002; COSMIC: COSV59184859; COSMIC: COSV59184859;