rs2042791

Variant names:

• chr2-213862497-A-C
• rs2042791
• NM_024532.5:c.1083A>C

Variant summary

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

The NM_024532.5(SPAG16):​c.1083A>C​(p.Gln361His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,613,432 control chromosomes in the GnomAD database, including 117,934 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.34 (9441 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108493 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.4257126E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG16	NM_024532.5	c.1083A>C	p.Gln361His	missense_variant	Exon 11 of 16	ENST00000331683.10	NP_078808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10	c.1083A>C	p.Gln361His	missense_variant	Exon 11 of 16	1	NM_024532.5	ENSP00000332592.5

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52145 AN: 151860 Hom.: 9442 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.390 AC: 97955 AN: 251166 Hom.: 19649 AF XY: 0.393 AC XY: 53386 AN XY: 135728

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.431

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.431

Gnomad SAS exome AF: 0.471

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.382 AC: 558305 AN: 1461454 Hom.: 108493 Cov.: 42 AF XY: 0.385 AC XY: 279619 AN XY: 727004

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.343 AC: 52161 AN: 151978 Hom.: 9441 Cov.: 32 AF XY: 0.350 AC XY: 25998 AN XY: 74280

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.334

Alfa AF: 0.370 Hom.: 27380

Bravo AF: 0.333

TwinsUK AF: 0.371 AC: 1375

ALSPAC AF: 0.374 AC: 1440

ESP6500AA AF: 0.229 AC: 1008

ESP6500EA AF: 0.378 AC: 3250

ExAC AF: 0.390 AC: 47387

Asia WGS AF: 0.478 AC: 1664 AN: 3478

EpiCase AF: 0.371

EpiControl AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.26
DANN	Benign	0.099
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.23	T;T
MetaRNN	Benign	0.00084	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.8	N;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	6.7	N;N
REVEL	Benign	0.089
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.079
MutPred		0.22		Loss of methylation at K364 (P = 0.1244);.;
MPC		0.021
ClinPred		0.00030	T
GERP RS		-1.4
Varity_R		0.034
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2042791; hg19: chr2-214727221; COSMIC: COSV59079144;