rs4658973

Variant names:

• chr1-117956431-T-G
• rs4658973
• NM_206996.4:c.*1-2382A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206996.4(SPAG17):​c.*1-2382A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,094 control chromosomes in the GnomAD database, including 10,599 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 0.34 (10599 hom., cov: 32)
• Consequence: SPAG17 NM_206996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG17	NM_206996.4	c.*1-2382A>C		intron_variant	Intron 48 of 48	ENST00000336338.10	NP_996879.1
WDR3	NM_006784.3	c.2454-637T>G		intron_variant	Intron 24 of 26	ENST00000349139.6	NP_006775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG17	ENST00000336338.10	c.*1-2382A>C		intron_variant	Intron 48 of 48	1	NM_206996.4	ENSP00000337804.5
WDR3	ENST00000349139.6	c.2454-637T>G		intron_variant	Intron 24 of 26	1	NM_006784.3	ENSP00000308179.4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51951 AN: 151974 Hom.: 10600 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 51954 AN: 152094 Hom.: 10599 Cov.: 32 AF XY: 0.342 AC XY: 25411 AN XY: 74322

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.350

Alfa AF: 0.425 Hom.: 7569

Bravo AF: 0.325

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs4658973; hg19: chr1-118499054;