rs80016542

Positions:

• chr2-214410302-G-A
• chr2-214410302-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024532.5(SPAG16):​c.1883G>A​(p.Arg628Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,598,342 control chromosomes in the GnomAD database, including 979 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.044 (528 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (451 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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]

SPAG16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017105341).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG16	NM_024532.5	c.1883G>A	p.Arg628Gln	missense_variant	16/16	ENST00000331683.10	NP_078808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10	c.1883G>A	p.Arg628Gln	missense_variant	16/16	1	NM_024532.5	ENSP00000332592.5

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6738 AN: 151992 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.0283

GnomAD3 exomes AF: 0.0112 AC: 2798 AN: 249588 Hom.: 199 AF XY: 0.00825 AC XY: 1113 AN XY: 134884

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.00656

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.00594

GnomAD4 exome AF: 0.00444 AC: 6427 AN: 1446232 Hom.: 451 Cov.: 31 AF XY: 0.00381 AC XY: 2729 AN XY: 715812

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.00770

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000268

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00859

GnomAD4 genome AF: 0.0444 AC: 6754 AN: 152110 Hom.: 528 Cov.: 32 AF XY: 0.0428 AC XY: 3181 AN XY: 74354

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.00784 Hom.: 137

Bravo AF: 0.0505

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.154 AC: 677

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.0138 AC: 1672

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000492

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	N;D
REVEL	Benign	0.086
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.17	B;.
Vest4		0.17
MPC		0.026
ClinPred		0.017	T
GERP RS		3.5
Varity_R		0.082
gMVP		0.31

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: rs80016542; hg19: chr2-215275026; COSMIC: COSV56968411; COSMIC: COSV56968411;