chr1-117981273-C-T

Variant names:

• chr1-117981273-C-T
• NM_206996.4:c.6001G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_206996.4(SPAG17):​c.6001G>A​(p.Glu2001Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,413,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SPAG17 NM_206996.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.812

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049826026).
• BP6: Variant 1-117981273-C-T is Benign according to our data. Variant chr1-117981273-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2323952.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG17	NM_206996.4	c.6001G>A	p.Glu2001Lys	missense_variant	Exon 43 of 49	ENST00000336338.10	NP_996879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG17	ENST00000336338.10	c.6001G>A	p.Glu2001Lys	missense_variant	Exon 43 of 49	1	NM_206996.4	ENSP00000337804.5
SPAG17	ENST00000437255.1	c.1441G>A	p.Glu481Lys	missense_variant	Exon 13 of 17	2		ENSP00000402749.1
SPAG17	ENST00000483383.1	n.491G>A		non_coding_transcript_exon_variant	Exon 4 of 5	3
SPAG17	ENST00000492438.5	n.298G>A		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1413300 Hom.: 0 Cov.: 30 AF XY: 0.00000285 AC XY: 2 AN XY: 702604

African (AFR) AF: 0.00 AC: 0 AN: 29788

American (AMR) AF: 0.00 AC: 0 AN: 29034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24342

East Asian (EAS) AF: 0.00 AC: 0 AN: 37502

South Asian (SAS) AF: 0.00 AC: 0 AN: 77440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1098184

Other (OTH) AF: 0.00 AC: 0 AN: 58344

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 08, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.17
DEOGEN2	Benign	0.0016	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		-0.81
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.014
Sift	Benign	0.48	T;T
Sift4G	Benign	0.96	T;T
Polyphen		0.0	B;.
Vest4		0.068
MutPred		0.13		Gain of ubiquitination at E2001 (P = 0.001);.;
MVP		0.030
MPC		0.053
ClinPred		0.044	T
GERP RS		-0.88
Varity_R		0.035
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

hg19: chr1-118523896;