19-5897599-T-C

Variant names:

• chr19-5897599-T-C
• rs10421538
• NM_175614.5:c.98-602A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175614.5(NDUFA11):​c.98-602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,168 control chromosomes in the GnomAD database, including 42,616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (42616 hom., cov: 33)
• Consequence: NDUFA11 NM_175614.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 3 publications found

Genes affected

NDUFA11 (HGNC:20371): (NADH:ubiquinone oxidoreductase subunit A11) This gene encodes a subunit of the membrane-bound mitochondrial complex I. Complex I is composed of numerous subunits and functions as the NADH-ubiquinol reductase of the mitochondrial electron transport chain. Mutations in this gene are associated with severe mitochondrial complex I deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

NDUFA11 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 14

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000267740 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175614.5. 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
	NDUFA11	NM_175614.5	MANE Select	c.98-602A>G		intron	N/A	NP_783313.1
	NDUFA11	NM_001193375.3		c.98-602A>G		intron	N/A	NP_001180304.1
	NDUFA11	NR_034166.3		n.300-602A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA11	ENST00000308961.5	TSL:1 MANE Select	c.98-602A>G		intron	N/A	ENSP00000311740.4
	ENSG00000267740	ENST00000585661.1	TSL:2	c.92-602A>G		intron	N/A	ENSP00000467210.1
	NDUFA11	ENST00000418389.7	TSL:2	c.98-602A>G		intron	N/A	ENSP00000389160.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113314 AN: 152048 Hom.: 42586 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.751

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.745 AC: 113398 AN: 152168 Hom.: 42616 Cov.: 33 AF XY: 0.748 AC XY: 55626 AN XY: 74400

African (AFR) AF: 0.651 AC: 27020 AN: 41500

American (AMR) AF: 0.829 AC: 12682 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2739 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3635 AN: 5162

South Asian (SAS) AF: 0.810 AC: 3909 AN: 4826

European-Finnish (FIN) AF: 0.738 AC: 7827 AN: 10608

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53043 AN: 67980

Other (OTH) AF: 0.751 AC: 1586 AN: 2112

Alfa AF: 0.778 Hom.: 70299

Bravo AF: 0.745

Asia WGS AF: 0.759 AC: 2639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		-0.17
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: rs10421538; hg19: chr19-5897610;