chr1-117963818-C-T

Position:

chr1-117963818-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_206996.4(SPAG17):c.6653G>A(p.Arg2218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,612,268 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2218C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0033 ( 33 hom. )

Consequence

SPAG17
NM_206996.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.448

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]

SPAG17 links:

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]

WDR3 links:

SPAG17 (HGNC:):

SPAG17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034430623).

BP6

Variant 1-117963818-C-T is Benign according to our data. Variant chr1-117963818-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038251.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG17	NM_206996.4 linkuse as main transcript	c.6653G>A	p.Arg2218His	missense_variant	48/49	ENST00000336338.10	NP_996879.1
WDR3	NM_006784.3 linkuse as main transcript	c.*4371C>T		3_prime_UTR_variant	27/27	ENST00000349139.6	NP_006775.1	Q9UNX4Q5TDG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG17	ENST00000336338.10 linkuse as main transcript	c.6653G>A	p.Arg2218His	missense_variant	48/49	1	NM_206996.4	ENSP00000337804.5		Q6Q759
WDR3	ENST00000349139.6 linkuse as main transcript	c.*4371C>T		3_prime_UTR_variant	27/27	1	NM_006784.3	ENSP00000308179.4		Q9UNX4

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

447

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00396

AC:

991

AN:

250058

Hom.:

AF XY:

0.00458

AC XY:

620

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00438

Gnomad AMR exome

AF:

0.00196

Gnomad ASJ exome

AF:

0.00420

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00334

AC:

4877

AN:

1460078

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

2667

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.00344

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.00357

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.000319

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00377

GnomAD4 genome

AF:

0.00296

AC:

451

AN:

152190

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.00334

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00312

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00430

AC:

522

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00351

EpiControl

AF:

0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SPAG17-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.0017

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.86

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.2

REVEL

Benign

0.012

Sift

Benign

0.13

Sift4G

Benign

0.11

Polyphen

0.012

Vest4

0.096

MVP

0.048

MPC

0.058

ClinPred

0.0040

GERP RS

-0.82

Varity_R

0.041

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over