rs2273581

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206996.4(SPAG17):​c.*170G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 770,682 control chromosomes in the GnomAD database, including 1,467 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 721 hom., cov: 32)
Exomes 𝑓: 0.026 ( 746 hom. )

Consequence

SPAG17
NM_206996.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.422
Variant links:
Genes affected
SPAG17 (HGNC:26620): (sperm associated antigen 17) This gene encodes a central pair protein present in the axonemes of cells with a "9 + 2" organization of microtubules. The encoded protein is required for the proper function of the axoneme. Mutations in the orthologous gene in mice lead to primary ciliary dyskinesia characterized by immotile nasal and tracheal cilia, reduced clearance of nasal mucus, profound respiratory distress, hydrocephalus, and neonatal lethality within twelve hours of birth due to impaired airway mucociliary clearance. Single-nucleotide polymorphisms in this gene are associated with human height and targeted mutations lead to skeletal malformations affecting the limbs in mice, suggesting a role for this gene in skeletal development. [provided by RefSeq, Feb 2017]
WDR3 (HGNC:12755): (WD repeat domain 3) This gene encodes a nuclear protein containing 10 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, which usually include a trp-asp at the C-terminal end. Proteins belonging to the WD repeat family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPAG17NM_206996.4 linkuse as main transcriptc.*170G>C 3_prime_UTR_variant 49/49 ENST00000336338.10 NP_996879.1
WDR3NM_006784.3 linkuse as main transcriptc.2269-127C>G intron_variant ENST00000349139.6 NP_006775.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPAG17ENST00000336338.10 linkuse as main transcriptc.*170G>C 3_prime_UTR_variant 49/491 NM_206996.4 ENSP00000337804 P1
WDR3ENST00000349139.6 linkuse as main transcriptc.2269-127C>G intron_variant 1 NM_006784.3 ENSP00000308179 P1

Frequencies

GnomAD3 genomes
AF:
0.0626
AC:
9517
AN:
152026
Hom.:
712
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.171
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0402
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.0819
Gnomad SAS
AF:
0.124
Gnomad FIN
AF:
0.00443
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0100
Gnomad OTH
AF:
0.0402
GnomAD4 exome
AF:
0.0265
AC:
16363
AN:
618538
Hom.:
746
Cov.:
9
AF XY:
0.0292
AC XY:
9422
AN XY:
322774
show subpopulations
Gnomad4 AFR exome
AF:
0.177
Gnomad4 AMR exome
AF:
0.0304
Gnomad4 ASJ exome
AF:
0.00191
Gnomad4 EAS exome
AF:
0.0751
Gnomad4 SAS exome
AF:
0.111
Gnomad4 FIN exome
AF:
0.00500
Gnomad4 NFE exome
AF:
0.00905
Gnomad4 OTH exome
AF:
0.0322
GnomAD4 genome
AF:
0.0628
AC:
9561
AN:
152144
Hom.:
721
Cov.:
32
AF XY:
0.0633
AC XY:
4711
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.171
Gnomad4 AMR
AF:
0.0401
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.0817
Gnomad4 SAS
AF:
0.123
Gnomad4 FIN
AF:
0.00443
Gnomad4 NFE
AF:
0.0100
Gnomad4 OTH
AF:
0.0398
Alfa
AF:
0.00640
Hom.:
4
Bravo
AF:
0.0676
Asia WGS
AF:
0.117
AC:
404
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.2
DANN
Benign
0.83

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: rs2273581; hg19: chr1-118496503; COSMIC: COSV60466396; API