rs12623569

Variant names:

• chr2-213930019-A-C
• rs12623569
• NM_024532.5:c.1274A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024532.5(SPAG16):​c.1274A>C​(p.Lys425Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,613,630 control chromosomes in the GnomAD database, including 57,836 homozygotes. 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: 𝑓 0.28 (6069 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51767 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 27 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004521936).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG16	NM_024532.5	c.1274A>C	p.Lys425Thr	missense_variant	Exon 12 of 16	ENST00000331683.10	NP_078808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10	c.1274A>C	p.Lys425Thr	missense_variant	Exon 12 of 16	1	NM_024532.5	ENSP00000332592.5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42182 AN: 151954 Hom.: 6070 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.270 AC: 67918 AN: 251282 AF XY: 0.261

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.451

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.262 AC: 382763 AN: 1461558 Hom.: 51767 Cov.: 34 AF XY: 0.258 AC XY: 187390 AN XY: 727076

African (AFR) AF: 0.277 AC: 9264 AN: 33466

American (AMR) AF: 0.295 AC: 13187 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9678 AN: 26132

East Asian (EAS) AF: 0.402 AC: 15962 AN: 39690

South Asian (SAS) AF: 0.132 AC: 11387 AN: 86240

European-Finnish (FIN) AF: 0.259 AC: 13820 AN: 53418

Middle Eastern (MID) AF: 0.289 AC: 1664 AN: 5766

European-Non Finnish (NFE) AF: 0.262 AC: 291001 AN: 1111748

Other (OTH) AF: 0.278 AC: 16800 AN: 60388

GnomAD4 genome AF: 0.277 AC: 42189 AN: 152072 Hom.: 6069 Cov.: 32 AF XY: 0.275 AC XY: 20446 AN XY: 74334

African (AFR) AF: 0.272 AC: 11290 AN: 41468

American (AMR) AF: 0.318 AC: 4862 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2235 AN: 5172

South Asian (SAS) AF: 0.127 AC: 613 AN: 4814

European-Finnish (FIN) AF: 0.269 AC: 2850 AN: 10576

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18126 AN: 67970

Other (OTH) AF: 0.313 AC: 662 AN: 2114

Alfa AF: 0.274 Hom.: 26337

Bravo AF: 0.284

TwinsUK AF: 0.264 AC: 979

ALSPAC AF: 0.265 AC: 1021

ESP6500AA AF: 0.272 AC: 1197

ESP6500EA AF: 0.262 AC: 2253

ExAC AF: 0.264 AC: 32099

Asia WGS AF: 0.269 AC: 936 AN: 3478

EpiCase AF: 0.276

EpiControl AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.88	N
PhyloP100		3.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Benign	0.095	T
Sift4G	Benign	0.12	T
Polyphen		0.0080	B
Vest4		0.11
MPC		0.023
ClinPred		0.013	T
GERP RS		4.3
Varity_R		0.16
gMVP		0.19
Mutation Taster		=81/19	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12623569; hg19: chr2-214794743; COSMIC: COSV59078990;