19-5897599-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000267740 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA11	NM_175614.5	c.98-602A>G		intron_variant	Intron 1 of 3	ENST00000308961.5	NP_783313.1
NDUFA11	NM_001193375.3	c.98-602A>G		intron_variant	Intron 1 of 3		NP_001180304.1
NDUFA11	NR_034166.3	n.300-602A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA11	ENST00000308961.5	c.98-602A>G		intron_variant	Intron 1 of 3	1	NM_175614.5	ENSP00000311740.4
ENSG00000267740	ENST00000586349.5	c.92-602A>G		intron_variant	Intron 1 of 3	2		ENSP00000466639.1

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

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.751

Alfa AF: 0.781 Hom.: 55710

Bravo AF: 0.745

Asia WGS AF: 0.759 AC: 2639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.57

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: rs10421538; hg19: chr19-5897610;