chr19-29212907-T-G

Variant names:

• chr19-29212907-T-G
• rs985046690
• NM_006003.3:c.212A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006003.3(UQCRFS1):​c.212A>C​(p.Asn71Thr) variant causes a missense, splice region 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. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N71S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UQCRFS1 NM_006003.3 missense, splice_region
• Scores: Splicing: ADA: 0.0001885
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.152659).

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.212A>C	p.Asn71Thr	missense splice_region	Exon 1 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.212A>C	p.Asn71Thr	missense splice_region	Exon 1 of 2	ENSP00000306397.3	P47985
	UQCRFS1	ENST00000933914.1		c.212A>C	p.Asn71Thr	missense splice_region	Exon 1 of 2	ENSP00000603973.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.079
Sift	Benign	0.28	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.42		Gain of sheet (P = 0.0827)
MVP		0.34
MPC		1.1
ClinPred		0.20	T
GERP RS		1.8
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.086
gMVP		0.48
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.0
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: rs985046690; hg19: chr19-29703814;