chr19-1391060-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024407.5(NDUFS7):c.408+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,612,552 control chromosomes in the GnomAD database, including 3,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 545 hom., cov: 33)

Exomes 𝑓: 0.042 ( 3418 hom. )

Consequence

NDUFS7
NM_024407.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.03

Publications

17 publications found

Variant links:

Genes affected

NDUFS7 (HGNC:7714): (NADH:ubiquinone oxidoreductase core subunit S7) This gene encodes a protein that is a subunit of one of the complexes that forms the mitochondrial respiratory chain. This protein is one of over 40 subunits found in complex I, the nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase. This complex functions in the transfer of electrons from NADH to the respiratory chain, and ubiquinone is believed to be the immediate electron acceptor for the enzyme. Mutations in this gene cause Leigh syndrome due to mitochondrial complex I deficiency, a severe neurological disorder that results in bilaterally symmetrical necrotic lesions in subcortical brain regions. [provided by RefSeq, Jul 2008]

NDUFS7 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency, nuclear type 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NDUFS7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-1391060-G-T is Benign according to our data. Variant chr19-1391060-G-T is described in ClinVar as Benign. ClinVar VariationId is 138498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024407.5. 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
	NDUFS7	NM_024407.5	MANE Select	c.408+10G>T		intron	N/A	NP_077718.3
	NDUFS7	NM_001363602.2		c.408+10G>T		intron	N/A	NP_001350531.1	F5H5N1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDUFS7	ENST00000233627.14	TSL:1 MANE Select	c.408+10G>T	intron	N/A	ENSP00000233627.9	O75251-1
NDUFS7	ENST00000874016.1		c.744+10G>T	intron	N/A	ENSP00000544075.1
NDUFS7	ENST00000874018.1		c.744+10G>T	intron	N/A	ENSP00000544077.1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9119

AN:

151920

Hom.:

540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0694

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0242

Gnomad OTH

AF:

0.0479

GnomAD2 exomes

AF:

0.0784

AC:

19390

AN:

247420

AF XY:

0.0747

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.0274

Gnomad EAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0526

GnomAD4 exome

AF:

0.0421

AC:

61501

AN:

1460514

Hom.:

3418

Cov.:

AF XY:

0.0436

AC XY:

31656

AN XY:

726598

show subpopulations

African (AFR)

AF:

0.0666

AC:

2229

AN:

33464

American (AMR)

AF:

0.174

AC:

7780

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.0267

AC:

697

AN:

26096

East Asian (EAS)

AF:

0.246

AC:

9759

AN:

39664

South Asian (SAS)

AF:

0.129

AC:

11126

AN:

86200

European-Finnish (FIN)

AF:

0.0119

AC:

625

AN:

52692

Middle Eastern (MID)

AF:

0.0265

AC:

153

AN:

5764

European-Non Finnish (NFE)

AF:

0.0234

AC:

26062

AN:

1111672

Other (OTH)

AF:

0.0509

AC:

3070

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4223

8446

12668

16891

21114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1290

2580

3870

5160

6450

<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:

0.0602

AC:

9159

AN:

152038

Hom.:

545

Cov.:

AF XY:

0.0643

AC XY:

4778

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0698

AC:

2895

AN:

41492

American (AMR)

AF:

0.151

AC:

2311

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

105

AN:

3460

East Asian (EAS)

AF:

0.250

AC:

1290

AN:

5170

South Asian (SAS)

AF:

0.140

AC:

675

AN:

4828

European-Finnish (FIN)

AF:

0.0106

AC:

112

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0242

AC:

1640

AN:

67886

Other (OTH)

AF:

0.0526

AC:

111

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

422

844

1265

1687

2109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0337

Hom.:

256

Bravo

AF:

0.0674

Asia WGS

AF:

0.210

AC:

729

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Leigh syndrome (1)

Mitochondrial complex I deficiency, nuclear type 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.18

(source)

DANN

Benign

0.75

PhyloP100

-2.0

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