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chr11-68036607-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002496.4(NDUFS8):​c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,862 control chromosomes in the GnomAD database, including 25,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2704 hom., cov: 33)
Exomes 𝑓: 0.17 ( 22411 hom. )

Consequence

NDUFS8
NM_002496.4 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.530
Variant links:
Genes affected
NDUFS8 (HGNC:7715): (NADH:ubiquinone oxidoreductase core subunit S8) This gene encodes a subunit of mitochondrial NADH:ubiquinone oxidoreductase, or Complex I, a multimeric enzyme of the respiratory chain responsible for NADH oxidation, ubiquinone reduction, and the ejection of protons from mitochondria. The encoded protein is involved in the binding of two of the six to eight iron-sulfur clusters of Complex I and, as such, is required in the electron transfer process. Mutations in this gene have been associated with Leigh syndrome. [provided by RefSeq, Mar 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 11-68036607-C-T is Benign according to our data. Variant chr11-68036607-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 305774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NDUFS8NM_002496.4 linkuse as main transcriptc.*14C>T 3_prime_UTR_variant 7/7 ENST00000313468.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NDUFS8ENST00000313468.10 linkuse as main transcriptc.*14C>T 3_prime_UTR_variant 7/71 NM_002496.4 P1
NDUFS8ENST00000528492.1 linkuse as main transcriptc.*14C>T 3_prime_UTR_variant 3/31
NDUFS8ENST00000531282.1 linkuse as main transcriptn.499C>T non_coding_transcript_exon_variant 2/22
NDUFS8ENST00000524810.5 linkuse as main transcriptc.*298C>T 3_prime_UTR_variant, NMD_transcript_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.182
AC:
27649
AN:
152128
Hom.:
2702
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.242
Gnomad AMI
AF:
0.240
Gnomad AMR
AF:
0.147
Gnomad ASJ
AF:
0.139
Gnomad EAS
AF:
0.145
Gnomad SAS
AF:
0.103
Gnomad FIN
AF:
0.0636
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.181
Gnomad OTH
AF:
0.189
GnomAD3 exomes
AF:
0.149
AC:
37255
AN:
249630
Hom.:
3116
AF XY:
0.148
AC XY:
20000
AN XY:
135328
show subpopulations
Gnomad AFR exome
AF:
0.242
Gnomad AMR exome
AF:
0.0998
Gnomad ASJ exome
AF:
0.150
Gnomad EAS exome
AF:
0.136
Gnomad SAS exome
AF:
0.103
Gnomad FIN exome
AF:
0.0711
Gnomad NFE exome
AF:
0.180
Gnomad OTH exome
AF:
0.164
GnomAD4 exome
AF:
0.171
AC:
249402
AN:
1460616
Hom.:
22411
Cov.:
33
AF XY:
0.169
AC XY:
122963
AN XY:
726588
show subpopulations
Gnomad4 AFR exome
AF:
0.247
Gnomad4 AMR exome
AF:
0.106
Gnomad4 ASJ exome
AF:
0.152
Gnomad4 EAS exome
AF:
0.161
Gnomad4 SAS exome
AF:
0.102
Gnomad4 FIN exome
AF:
0.0769
Gnomad4 NFE exome
AF:
0.182
Gnomad4 OTH exome
AF:
0.166
GnomAD4 genome
AF:
0.182
AC:
27662
AN:
152246
Hom.:
2704
Cov.:
33
AF XY:
0.175
AC XY:
12998
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.241
Gnomad4 AMR
AF:
0.147
Gnomad4 ASJ
AF:
0.139
Gnomad4 EAS
AF:
0.145
Gnomad4 SAS
AF:
0.103
Gnomad4 FIN
AF:
0.0636
Gnomad4 NFE
AF:
0.181
Gnomad4 OTH
AF:
0.188
Alfa
AF:
0.174
Hom.:
988
Bravo
AF:
0.192
Asia WGS
AF:
0.136
AC:
471
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Mitochondrial complex I deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Mitochondrial complex I deficiency, nuclear type 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Leigh syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Osteopetrosis Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
2.3
DANN
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1051806; hg19: chr11-67804074; COSMIC: COSV55834957; COSMIC: COSV55834957; API