chr2-213350614-C-G

Variant names:

• chr2-213350614-C-G
• rs528853880
• NM_024532.5:c.731C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024532.5(SPAG16):​c.731C>G​(p.Thr244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T244I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38903698).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	NM_024532.5	MANE Select	c.731C>G	p.Thr244Ser	missense	Exon 7 of 16	NP_078808.3
	SPAG16	NR_047659.2		n.926C>G		non_coding_transcript_exon	Exon 9 of 18
	SPAG16	NR_047660.2		n.632C>G		non_coding_transcript_exon	Exon 6 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.731C>G	p.Thr244Ser	missense	Exon 7 of 16	ENSP00000332592.5	Q8N0X2-1
	SPAG16	ENST00000447990.1	TSL:1	c.731C>G	p.Thr244Ser	missense	Exon 7 of 10	ENSP00000400847.1	E7EWV3
	SPAG16	ENST00000406979.6	TSL:1	n.*732C>G		non_coding_transcript_exon	Exon 9 of 18	ENSP00000385496.2	F8WB32

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449060 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720726

African (AFR) AF: 0.00 AC: 0 AN: 32854

American (AMR) AF: 0.00 AC: 0 AN: 41724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25716

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39206

South Asian (SAS) AF: 0.00 AC: 0 AN: 83380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107462

Other (OTH) AF: 0.00 AC: 0 AN: 59864

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Benign	0.086	T
Polyphen		0.73	P
Vest4		0.50
MutPred		0.65		Gain of sheet (P = 0.0221)
MVP		0.72
MPC		0.030
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.094
gMVP		0.059
Mutation Taster		=87/13	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: rs528853880; hg19: chr2-214215338;