rs3213975
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_016616.5(NME8):āc.1603T>Cā(p.Leu535=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,196 control chromosomes in the GnomAD database, including 44,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.23 ( 3886 hom., cov: 31)
Exomes š: 0.23 ( 40147 hom. )
Consequence
NME8
NM_016616.5 synonymous
NM_016616.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.314
Genes affected
NME8 (HGNC:16473): (NME/NM23 family member 8) This gene encodes a protein with an N-terminal thioredoxin domain and three C-terminal nucleoside diphosphate kinase (NDK) domains, but the NDK domains are thought to be catalytically inactive. The sea urchin ortholog of this gene encodes a component of sperm outer dynein arms, and the protein is implicated in ciliary function. Mutations in this gene are implicated in primary ciliary dyskinesia type 6.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 7-37896928-T-C is Benign according to our data. Variant chr7-37896928-T-C is described in ClinVar as [Benign]. Clinvar id is 164806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.314 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NME8 | NM_016616.5 | c.1603T>C | p.Leu535= | synonymous_variant | 17/18 | ENST00000199447.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NME8 | ENST00000199447.9 | c.1603T>C | p.Leu535= | synonymous_variant | 17/18 | 1 | NM_016616.5 | P1 | |
NME8 | ENST00000440017.5 | c.1603T>C | p.Leu535= | synonymous_variant | 16/16 | 1 | P1 | ||
NME8 | ENST00000476435.1 | n.112T>C | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.227 AC: 34381AN: 151760Hom.: 3883 Cov.: 31
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GnomAD3 exomes AF: 0.242 AC: 60776AN: 251196Hom.: 7563 AF XY: 0.244 AC XY: 33121AN XY: 135744
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GnomAD4 exome AF: 0.233 AC: 340358AN: 1461318Hom.: 40147 Cov.: 35 AF XY: 0.233 AC XY: 169736AN XY: 726982
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GnomAD4 genome ? AF: 0.227 AC: 34408AN: 151878Hom.: 3886 Cov.: 31 AF XY: 0.227 AC XY: 16847AN XY: 74200
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Leu535Leu in exon 17 of TXNDC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 24.2% (2077/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3213975). - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 01, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Primary ciliary dyskinesia 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at