rs2598044
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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):c.177C>T(p.Asp59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,605,020 control chromosomes in the GnomAD database, including 49,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.28 ( 6014 hom., cov: 33)
Exomes 𝑓: 0.24 ( 43970 hom. )
Consequence
NME8
NM_016616.5 synonymous
NM_016616.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.953
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=-0.68).
BP6
?
Variant 7-37850714-C-T is Benign according to our data. Variant chr7-37850714-C-T is described in ClinVar as [Benign]. Clinvar id is 164799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.953 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NME8 | NM_016616.5 | c.177C>T | p.Asp59= | synonymous_variant | 5/18 | ENST00000199447.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NME8 | ENST00000199447.9 | c.177C>T | p.Asp59= | synonymous_variant | 5/18 | 1 | NM_016616.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.275 AC: 41818AN: 151936Hom.: 6003 Cov.: 33
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GnomAD3 exomes AF: 0.229 AC: 57476AN: 250792Hom.: 7102 AF XY: 0.224 AC XY: 30324AN XY: 135520
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GnomAD4 exome AF: 0.241 AC: 349803AN: 1452966Hom.: 43970 Cov.: 31 AF XY: 0.238 AC XY: 172214AN XY: 723382
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GnomAD4 genome ? AF: 0.275 AC: 41860AN: 152054Hom.: 6014 Cov.: 33 AF XY: 0.272 AC XY: 20220AN XY: 74332
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Asp59Asp in exon 5 of TXNDC3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 36.8% (1622/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2598044). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia 6 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 10, 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 | May 04, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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