rs75531720
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_016616.5(NME8):c.271-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,564,850 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0050 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 4 hom. )
Consequence
NME8
NM_016616.5 splice_polypyrimidine_tract, intron
NM_016616.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0630
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 7-37862014-C-T is Benign according to our data. Variant chr7-37862014-C-T is described in ClinVar as [Benign]. Clinvar id is 226854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00495 (754/152264) while in subpopulation AFR AF= 0.0169 (701/41564). AF 95% confidence interval is 0.0158. There are 9 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NME8 | NM_016616.5 | c.271-14C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000199447.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NME8 | ENST00000199447.9 | c.271-14C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_016616.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00495 AC: 753AN: 152146Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00153 AC: 384AN: 250838Hom.: 4 AF XY: 0.00109 AC XY: 148AN XY: 135586
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GnomAD4 exome AF: 0.000582 AC: 822AN: 1412586Hom.: 4 Cov.: 27 AF XY: 0.000476 AC XY: 336AN XY: 705704
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GnomAD4 genome ? AF: 0.00495 AC: 754AN: 152264Hom.: 9 Cov.: 32 AF XY: 0.00481 AC XY: 358AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:3
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 | 271-14C>T in intron 6 of TXNDC3: This variant is not expected to have clinical s ignificance because it has been identified in 1.8% (79/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs75531720). - |
Primary ciliary dyskinesia 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
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