16-1959761-A-G

Variant names:

• chr16-1959761-A-G
• rs4402569
• NM_004548.3:c.130+7A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004548.3(NDUFB10):​c.130+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,612,626 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (171 hom., cov: 33)
  • Exomes 𝑓: 0.028 (699 hom.)
• Consequence: NDUFB10 NM_004548.3 splice_region, intron
• Scores: Splicing: ADA: 0.0003757
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.352
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-1959761-A-G is Benign according to our data. Variant chr16-1959761-A-G is described in ClinVar as Benign. ClinVar VariationId is 2123710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0752 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB10	NM_004548.3	MANE Select	c.130+7A>G		splice_region intron	N/A	NP_004539.1	A8K761

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB10	ENST00000268668.11	TSL:1 MANE Select	c.130+7A>G		splice_region intron	N/A	ENSP00000268668.6	O96000-1
	NDUFB10	ENST00000543683.6	TSL:1	c.130+7A>G		splice_region intron	N/A	ENSP00000445086.2	O96000-2
	NDUFB10	ENST00000926882.1		c.130+7A>G		splice_region intron	N/A	ENSP00000596941.1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5780 AN: 151990 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0252 AC: 6269 AN: 248364 AF XY: 0.0252

Gnomad AFR exome AF: 0.0794

Gnomad AMR exome AF: 0.00898

Gnomad ASJ exome AF: 0.00991

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.0284

Gnomad OTH exome AF: 0.0223

GnomAD4 exome AF: 0.0282 AC: 41256 AN: 1460518 Hom.: 699 Cov.: 31 AF XY: 0.0279 AC XY: 20304 AN XY: 726568

African (AFR) AF: 0.0779 AC: 2605 AN: 33454

American (AMR) AF: 0.0103 AC: 460 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 290 AN: 26084

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39654

South Asian (SAS) AF: 0.0312 AC: 2694 AN: 86232

European-Finnish (FIN) AF: 0.0143 AC: 756 AN: 52738

Middle Eastern (MID) AF: 0.0213 AC: 123 AN: 5764

European-Non Finnish (NFE) AF: 0.0293 AC: 32576 AN: 1111556

Other (OTH) AF: 0.0289 AC: 1747 AN: 60348

GnomAD4 genome AF: 0.0381 AC: 5790 AN: 152108 Hom.: 171 Cov.: 33 AF XY: 0.0369 AC XY: 2741 AN XY: 74358

African (AFR) AF: 0.0774 AC: 3212 AN: 41486

American (AMR) AF: 0.0182 AC: 278 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0372 AC: 179 AN: 4814

European-Finnish (FIN) AF: 0.0149 AC: 158 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1831 AN: 67942

Other (OTH) AF: 0.0260 AC: 55 AN: 2114

Alfa AF: 0.0312 Hom.: 56

Bravo AF: 0.0391

Asia WGS AF: 0.0150 AC: 54 AN: 3478

EpiCase AF: 0.0232

EpiControl AF: 0.0244

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.51
PhyloP100		-0.35
PromoterAI		0.13	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00038
dbscSNV1_RF	Benign	0.0020
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: rs4402569; hg19: chr16-2009762;