rs1555198835

Variant names:

• chr11-47580872-C-A
• NM_004551.3:c.269C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47580872-C-A
• chr11-47580872-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004551.3(NDUFS3):​c.269C>A​(p.Pro90His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDUFS3 NM_004551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFS3	NM_004551.3	c.269C>A	p.Pro90His	missense_variant	Exon 4 of 7	ENST00000263774.9	NP_004542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFS3	ENST00000263774.9	c.269C>A	p.Pro90His	missense_variant	Exon 4 of 7	1	NM_004551.3	ENSP00000263774.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;T;D;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	3.2	M;.;.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-8.1	D;D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0080	D;D;T;D
Polyphen		0.030	B;.;.;.
Vest4		0.86
MutPred		0.54		Gain of catalytic residue at I88 (P = 0.0959);Gain of catalytic residue at I88 (P = 0.0959);.;Gain of catalytic residue at I88 (P = 0.0959);
MVP		0.99
MPC		1.1
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.95
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47602424;