NM_024532.5:c.890G>C

Variant names:

• chr2-213375067-G-C
• rs747636240
• NM_024532.5:c.890G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024532.5(SPAG16):​c.890G>C​(p.Arg297Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16735944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG16	NM_024532.5	c.890G>C	p.Arg297Pro	missense_variant	Exon 9 of 16	ENST00000331683.10	NP_078808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10	c.890G>C	p.Arg297Pro	missense_variant	Exon 9 of 16	1	NM_024532.5	ENSP00000332592.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 248038 Hom.: 0 AF XY: 0.0000224 AC XY: 3 AN XY: 134204

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458112 Hom.: 0 Cov.: 29 AF XY: 0.00000827 AC XY: 6 AN XY: 725362

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000818

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.012	D;T;D
Sift4G	Uncertain	0.031	D;T;D
Polyphen		0.61	.;P;.
Vest4		0.70, 0.52
MutPred		0.44		Loss of MoRF binding (P = 0.0035);Loss of MoRF binding (P = 0.0035);Loss of MoRF binding (P = 0.0035);
MVP		0.62
MPC		0.025
ClinPred		0.16	T
GERP RS		1.3
Varity_R		0.43
gMVP		0.24

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

Other links and lift over

dbSNP: rs747636240; hg19: chr2-214239791;