rs12988374

Variant names:

• chr2-214410278-C-T
• rs12988374
• NM_024532.5:c.1859C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024532.5(SPAG16):​c.1859C>T​(p.Ser620Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• Publications: 1 publications found

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]

ENSG00000197585 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024532.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	NM_024532.5	MANE Select	c.1859C>T	p.Ser620Phe	missense	Exon 16 of 16	NP_078808.3
	SPAG16	NR_047659.2		n.2054C>T		non_coding_transcript_exon	Exon 18 of 18
	SPAG16	NR_047660.2		n.1760C>T		non_coding_transcript_exon	Exon 15 of 15

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.1859C>T	p.Ser620Phe	missense	Exon 16 of 16	ENSP00000332592.5
	SPAG16	ENST00000406979.6	TSL:1	n.*1860C>T		non_coding_transcript_exon	Exon 18 of 18	ENSP00000385496.2
	SPAG16	ENST00000406979.6	TSL:1	n.*1860C>T		3_prime_UTR	Exon 18 of 18	ENSP00000385496.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		4.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.57		Loss of glycosylation at S620 (P = 0.0063)
MVP		0.91
MPC		0.19
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.52
gMVP		0.74
Mutation Taster		=66/34	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

Other links and lift over

dbSNP: rs12988374; hg19: chr2-215275002;