NDUFA13 p.Pro12Pro

Variant names:

• chr19-19516271-T-T
• ENST00000507754.9:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-19516272--
• chr19-19516274-G-T
• chr19-19516274-G-C
• chr19-19516274-G-A

Variant summary

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

The ENST00000507754.9(NDUFA13):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDUFA13 ENST00000507754.9 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31
• Publications: 0 publications found

Genes affected

NDUFA13 (HGNC:17194): (NADH:ubiquinone oxidoreductase subunit A13) This gene encodes a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. The protein is required for complex I assembly and electron transfer activity. The protein binds the signal transducers and activators of transcription 3 (STAT3) transcription factor, and can function as a tumor suppressor. The human protein purified from mitochondria migrates at approximately 16 kDa. Transcripts originating from an upstream promoter and capable of expressing a protein with a longer N-terminus have been found, but their biological validity has not been determined. [provided by RefSeq, Oct 2009]

NDUFA13 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex I deficiency, nuclear type 28

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• thyroid Hurthle cell carcinoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000258674 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000507754.9. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA13	ENST00000507754.9	TSL:1 MANE Select	c.		exon_region	Exon 1 of 5	ENSP00000423673.1	Q9P0J0-1
	ENSG00000258674	ENST00000555938.1	TSL:2	c.		exon_region	Exon 1 of 7	ENSP00000452549.1	E7ENQ6
	NDUFA13	ENST00000911745.1		c.		exon_region	Exon 1 of 6	ENSP00000581804.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-19627080;