16-1961125-A-G

Variant names:

• chr16-1961125-A-G
• rs758335
• NM_004548.3:c.131-28A>G

Variant summary

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

The NM_004548.3(NDUFB10):​c.131-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,611,806 control chromosomes in the GnomAD database, including 544,446 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 0.86 (56770 hom., cov: 35)
  • Exomes 𝑓: 0.82 (487676 hom.)
• Consequence: NDUFB10 NM_004548.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 33 publications found

Genes affected

NDUFB10 (HGNC:7696): (NADH:ubiquinone oxidoreductase subunit B10) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 35. [provided by Alliance of Genome Resources, Apr 2022]

NDUFB10 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex 1 deficiency, nuclear type 35

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004548.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB10	NM_004548.3	MANE Select	c.131-28A>G		intron	N/A	NP_004539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB10	ENST00000268668.11	TSL:1 MANE Select	c.131-28A>G		intron	N/A	ENSP00000268668.6
	NDUFB10	ENST00000543683.6	TSL:1	c.131-28A>G		intron	N/A	ENSP00000445086.2
	NDUFB10	ENST00000569148.1	TSL:2	c.131-28A>G		intron	N/A	ENSP00000455348.1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130901 AN: 152202 Hom.: 56726 Cov.: 35

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.832

GnomAD2 exomes AF: 0.820 AC: 205346 AN: 250296 AF XY: 0.822

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.698

Gnomad ASJ exome AF: 0.809

Gnomad EAS exome AF: 0.893

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.814

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.816 AC: 1191278 AN: 1459486 Hom.: 487676 Cov.: 44 AF XY: 0.817 AC XY: 592797 AN XY: 725874

African (AFR) AF: 0.969 AC: 32398 AN: 33434

American (AMR) AF: 0.710 AC: 31711 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 20969 AN: 26092

East Asian (EAS) AF: 0.843 AC: 33453 AN: 39674

South Asian (SAS) AF: 0.823 AC: 70910 AN: 86162

European-Finnish (FIN) AF: 0.887 AC: 47252 AN: 53296

Middle Eastern (MID) AF: 0.853 AC: 4513 AN: 5290

European-Non Finnish (NFE) AF: 0.811 AC: 900371 AN: 1110638

Other (OTH) AF: 0.825 AC: 49701 AN: 60260

GnomAD4 genome AF: 0.860 AC: 131005 AN: 152320 Hom.: 56770 Cov.: 35 AF XY: 0.861 AC XY: 64154 AN XY: 74472

African (AFR) AF: 0.960 AC: 39911 AN: 41574

American (AMR) AF: 0.764 AC: 11687 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2779 AN: 3472

East Asian (EAS) AF: 0.887 AC: 4593 AN: 5176

South Asian (SAS) AF: 0.819 AC: 3956 AN: 4830

European-Finnish (FIN) AF: 0.891 AC: 9458 AN: 10618

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55794 AN: 68034

Other (OTH) AF: 0.831 AC: 1759 AN: 2116

Alfa AF: 0.816 Hom.: 47154

Bravo AF: 0.851

Asia WGS AF: 0.837 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.31
DANN	Benign	0.39
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758335; hg19: chr16-2011126;