21-42903486-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_021075.4(NDUFV3):c.474C>T(p.Ser158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
NDUFV3
NM_021075.4 synonymous
NM_021075.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.38
Genes affected
NDUFV3 (HGNC:7719): (NADH:ubiquinone oxidoreductase subunit V3) The protein encoded by this gene is one of at least forty-one subunits that make up the NADH-ubiquinone oxidoreductase complex. This complex is part of the mitochondrial respiratory chain and serves to catalyze the rotenone-sensitive oxidation of NADH and the reduction of ubiquinone. The encoded protein is one of three proteins found in the flavoprotein fraction of the complex. The specific function of the encoded protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 21-42903486-C-T is Benign according to our data. Variant chr21-42903486-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048046.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=1.38 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFV3 | NM_021075.4 | c.474C>T | p.Ser158= | synonymous_variant | 3/4 | ENST00000354250.7 | NP_066553.3 | |
NDUFV3 | XM_011529586.3 | c.474C>T | p.Ser158= | synonymous_variant | 3/5 | XP_011527888.1 | ||
NDUFV3 | NM_001001503.2 | c.170-5378C>T | intron_variant | NP_001001503.1 | ||||
NDUFV3 | XM_017028359.2 | c.170-3354C>T | intron_variant | XP_016883848.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDUFV3 | ENST00000354250.7 | c.474C>T | p.Ser158= | synonymous_variant | 3/4 | 1 | NM_021075.4 | ENSP00000346196 | ||
NDUFV3 | ENST00000340344.4 | c.170-5378C>T | intron_variant | 1 | ENSP00000342895 | P1 | ||||
NDUFV3 | ENST00000460259.1 | n.997C>T | non_coding_transcript_exon_variant | 5/6 | 2 | |||||
NDUFV3 | ENST00000460740.1 | n.366C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251422Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461742Hom.: 0 Cov.: 76 AF XY: 0.00000413 AC XY: 3AN XY: 727164
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
NDUFV3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 27, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at