NM_006003.3:c.471C>T

Variant names:

• chr19-29207902-G-A
• rs4805344
• NM_006003.3:c.471C>T

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.471C>T​(p.Ser157Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,613,898 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (100 hom.)
• Consequence: UQCRFS1 NM_006003.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55
• Publications: 2 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 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex III deficiency, nuclear type 10

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-29207902-G-A is Benign according to our data. Variant chr19-29207902-G-A is described in ClinVar as Benign. ClinVar VariationId is 789459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

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.471C>T	p.Ser157Ser	synonymous	Exon 2 of 2	NP_005994.2	P47985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRFS1	ENST00000304863.6	TSL:1 MANE Select	c.471C>T	p.Ser157Ser	synonymous	Exon 2 of 2	ENSP00000306397.3	P47985
	UQCRFS1	ENST00000933914.1		c.441C>T	p.Ser147Ser	synonymous	Exon 2 of 2	ENSP00000603973.1

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 504 AN: 152130 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00910 AC: 2279 AN: 250486 AF XY: 0.00766

Gnomad AFR exome AF: 0.0000628

Gnomad AMR exome AF: 0.0325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0535

Gnomad FIN exome AF: 0.00347

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00475

GnomAD4 exome AF: 0.00305 AC: 4457 AN: 1461650 Hom.: 100 Cov.: 31 AF XY: 0.00286 AC XY: 2083 AN XY: 727134

African (AFR) AF: 0.000179 AC: 6 AN: 33472

American (AMR) AF: 0.0295 AC: 1321 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0622 AC: 2470 AN: 39698

South Asian (SAS) AF: 0.00167 AC: 144 AN: 86244

European-Finnish (FIN) AF: 0.00359 AC: 192 AN: 53416

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5762

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1111838

Other (OTH) AF: 0.00238 AC: 144 AN: 60378

GnomAD4 genome AF: 0.00332 AC: 505 AN: 152248 Hom.: 11 Cov.: 33 AF XY: 0.00371 AC XY: 276 AN XY: 74422

African (AFR) AF: 0.000241 AC: 10 AN: 41550

American (AMR) AF: 0.0102 AC: 156 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0496 AC: 257 AN: 5180

South Asian (SAS) AF: 0.00519 AC: 25 AN: 4818

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68028

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00109 Hom.: 1

Bravo AF: 0.00491

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.54
PhyloP100		-1.5
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

Other links and lift over

dbSNP: rs4805344; hg19: chr19-29698809;