chr2-213296103-A-G

Position:

• chr2-213296103-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024532.5(SPAG16):​c.176A>G​(p.Tyr59Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

Genes affected

SPAG16 (HGNC:23225): (sperm associated antigen 16) Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG16	NM_024532.5	c.176A>G	p.Tyr59Cys	missense_variant	2/16	ENST00000331683.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG16	ENST00000331683.10	c.176A>G	p.Tyr59Cys	missense_variant	2/16	1	NM_024532.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.176A>G (p.Y59C) alteration is located in exon 2 (coding exon 2) of the SPAG16 gene. This alteration results from a A to G substitution at nucleotide position 176, causing the tyrosine (Y) at amino acid position 59 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.60	T
MutationTaster	Benign	0.99	D;D;D;D;D;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D
Vest4		0.78, 0.81, 0.81
MutPred		0.39		Loss of phosphorylation at Y59 (P = 0.0034);Loss of phosphorylation at Y59 (P = 0.0034);Loss of phosphorylation at Y59 (P = 0.0034);Loss of phosphorylation at Y59 (P = 0.0034);
MVP		0.84
MPC		0.19
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.36
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-214160827;