chr1-117953880-C-G

Variant names:

• chr1-117953880-C-G
• rs2273581
• NM_206996.4:c.*170G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPAG17	NM_206996.4	c.*170G>C		3_prime_UTR_variant	Exon 49 of 49	ENST00000336338.10	NP_996879.1
WDR3	NM_006784.3	c.2269-127C>G		intron_variant	Intron 21 of 26	ENST00000349139.6	NP_006775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG17	ENST00000336338	c.*170G>C		3_prime_UTR_variant	Exon 49 of 49	1	NM_206996.4	ENSP00000337804.5
WDR3	ENST00000349139.6	c.2269-127C>G		intron_variant	Intron 21 of 26	1	NM_006784.3	ENSP00000308179.4

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9517 AN: 152026 Hom.: 712 Cov.: 32

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

Gnomad4 AFR exome AF: 0.177 AC: 2815 AN: 15920

Gnomad4 AMR exome AF: 0.0304 AC: 632 AN: 20814

Gnomad4 ASJ exome AF: 0.00191 AC: 28 AN: 14640

Gnomad4 EAS exome AF: 0.0751 AC: 2602 AN: 34634

Gnomad4 SAS exome AF: 0.111 AC: 5324 AN: 47946

Gnomad4 FIN exome AF: 0.00500 AC: 215 AN: 43016

Gnomad4 NFE exome AF: 0.00905 AC: 3675 AN: 406046

Gnomad4 Remaining exome AF: 0.0322 AC: 1021 AN: 31738

GnomAD4 genome AF: 0.0628 AC: 9561 AN: 152144 Hom.: 721 Cov.: 32 AF XY: 0.0633 AC XY: 4711 AN XY: 74390

Gnomad4 AFR AF: 0.171 AC: 0.171204 AN: 0.171204

Gnomad4 AMR AF: 0.0401 AC: 0.0401283 AN: 0.0401283

Gnomad4 ASJ AF: 0.00144 AC: 0.00144175 AN: 0.00144175

Gnomad4 EAS AF: 0.0817 AC: 0.0816918 AN: 0.0816918

Gnomad4 SAS AF: 0.123 AC: 0.122873 AN: 0.122873

Gnomad4 FIN AF: 0.00443 AC: 0.00442978 AN: 0.00442978

Gnomad4 NFE AF: 0.0100 AC: 0.0100197 AN: 0.0100197

Gnomad4 OTH AF: 0.0398 AC: 0.0398104 AN: 0.0398104

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
Mutation Taster		=100/0	polymorphism (auto)

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