chr11-47580595-C-G

Position:

• chr11-47580595-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004551.3(NDUFS3):​c.204C>G​(p.Ile68Met) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDUFS3 NM_004551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

Genes affected

NDUFS3 (HGNC:7710): (NADH:ubiquinone oxidoreductase core subunit S3) This gene encodes one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone oxidoreductase (complex I). Mutations in this gene are associated with Leigh syndrome resulting from mitochondrial complex I deficiency.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2759636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS3	NM_004551.3	c.204C>G	p.Ile68Met	missense_variant	3/7	ENST00000263774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS3	ENST00000263774.9	c.204C>G	p.Ile68Met	missense_variant	3/7	1	NM_004551.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome;C1838979:Mitochondrial complex I deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital

Nov 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T;T;T;T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Uncertain	-0.082	T
MutationAssessor	Benign	1.5	L;.;.;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.54	N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.10	B;.;.;.;.
Vest4		0.29
MutPred		0.43		Loss of catalytic residue at P70 (P = 0.0303);Loss of catalytic residue at P70 (P = 0.0303);.;Loss of catalytic residue at P70 (P = 0.0303);Loss of catalytic residue at P70 (P = 0.0303);
MVP		0.93
MPC		0.32
ClinPred		0.65	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.41

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: rs886044765; hg19: chr11-47602147;