NM_006003.3:c.24A>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006003.3(UQCRFS1):​c.24A>T​(p.Ser8Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 37)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UQCRFS1 NM_006003.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• Publications: 15 publications found

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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006003.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRFS1	NM_006003.3	MANE Select	c.24A>T	p.Ser8Ser	synonymous	Exon 1 of 2	NP_005994.2	P47985
	UQCRFS1-DT	NR_184021.1		n.-158T>A		upstream_gene	N/A
	UQCRFS1-DT	NR_184022.1		n.-158T>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRFS1	ENST00000304863.6	TSL:1 MANE Select	c.24A>T	p.Ser8Ser	synonymous	Exon 1 of 2	ENSP00000306397.3	P47985
	UQCRFS1	ENST00000933914.1		c.24A>T	p.Ser8Ser	synonymous	Exon 1 of 2	ENSP00000603973.1
	UQCRFS1-DT	ENST00000587859.2	TSL:2	n.-113T>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1357844 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 670032

African (AFR) AF: 0.00 AC: 0 AN: 27934

American (AMR) AF: 0.00 AC: 0 AN: 33236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24124

East Asian (EAS) AF: 0.00 AC: 0 AN: 31764

South Asian (SAS) AF: 0.00 AC: 0 AN: 77732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068524

Other (OTH) AF: 0.00 AC: 0 AN: 56662

GnomAD4 genome Cov.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.3
DANN	Benign	0.57
PhyloP100		-0.65
PromoterAI		-0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs11666764; hg19: chr19-29704002;