Genetic Variant NM_004548.3:c.72C>T (chr16-1959696-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004548.3(NDUFB10):c.72C>T(p.Ile24Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,613,348 control chromosomes in the GnomAD database, including 3,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.070 ( 789 hom., cov: 33)

Exomes 𝑓: 0.031 ( 2801 hom. )

Consequence

NDUFB10
NM_004548.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.261

Publications

15 publications found

Variant links:

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)

NDUFB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 16-1959696-C-T is Benign according to our data. Variant chr16-1959696-C-T is described in ClinVar as Benign. ClinVar VariationId is 2014724.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.261 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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.72C>T	p.Ile24Ile	synonymous	Exon 1 of 4	NP_004539.1	A8K761

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFB10	ENST00000268668.11	TSL:1 MANE Select	c.72C>T	p.Ile24Ile	synonymous	Exon 1 of 4	ENSP00000268668.6	O96000-1
NDUFB10	ENST00000543683.6	TSL:1	c.72C>T	p.Ile24Ile	synonymous	Exon 1 of 3	ENSP00000445086.2	O96000-2
NDUFB10	ENST00000926882.1		c.72C>T	p.Ile24Ile	synonymous	Exon 1 of 4	ENSP00000596941.1

Frequencies

GnomAD3 genomes

AF:

0.0705

AC:

10725

AN:

152078

Hom.:

791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0511

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.0458

Gnomad FIN

AF:

0.0508

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0675

GnomAD2 exomes

AF:

0.0575

AC:

14384

AN:

250350

AF XY:

0.0535

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0389

Gnomad ASJ exome

AF:

0.0352

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.0517

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

AF:

0.0305

AC:

44570

AN:

1461152

Hom.:

2801

Cov.:

AF XY:

0.0304

AC XY:

22095

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.156

AC:

5213

AN:

33456

American (AMR)

AF:

0.0407

AC:

1818

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0336

AC:

878

AN:

26114

East Asian (EAS)

AF:

0.305

AC:

12086

AN:

39674

South Asian (SAS)

AF:

0.0400

AC:

3452

AN:

86248

European-Finnish (FIN)

AF:

0.0481

AC:

2550

AN:

53030

Middle Eastern (MID)

AF:

0.0513

AC:

296

AN:

5768

European-Non Finnish (NFE)

AF:

0.0141

AC:

15629

AN:

1111786

Other (OTH)

AF:

0.0439

AC:

2648

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2062

4124

6186

8248

10310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0705

AC:

10725

AN:

152196

Hom.:

789

Cov.:

AF XY:

0.0728

AC XY:

5417

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.149

AC:

6187

AN:

41514

American (AMR)

AF:

0.0510

AC:

781

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3472

East Asian (EAS)

AF:

0.306

AC:

1576

AN:

5150

South Asian (SAS)

AF:

0.0456

AC:

220

AN:

4826

European-Finnish (FIN)

AF:

0.0508

AC:

539

AN:

10620

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0170

AC:

1156

AN:

67992

Other (OTH)

AF:

0.0672

AC:

142

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

476

953

1429

1906

2382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0344

Hom.:

829

Bravo

AF:

0.0770

Asia WGS

AF:

0.131

AC:

455

AN:

3478

EpiCase

AF:

0.0209

EpiControl

AF:

0.0205

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.1

(source)

DANN

Benign

0.86

PhyloP100

0.26

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over