chr2-213862497-A-C

Variant names:

• chr2-213862497-A-C
• rs2042791
• NM_024532.5:c.1083A>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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q361Q) has been classified as Uncertain significance.

• 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
• Publications: 32 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=8.4257126E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

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.1083A>C	p.Gln361His	missense	Exon 11 of 16	NP_078808.3
	SPAG16	NR_047659.2		n.1278A>C		non_coding_transcript_exon	Exon 13 of 18
	SPAG16	NR_047660.2		n.984A>C		non_coding_transcript_exon	Exon 10 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.1083A>C	p.Gln361His	missense	Exon 11 of 16	ENSP00000332592.5
	SPAG16	ENST00000406979.6	TSL:1	n.*1084A>C		non_coding_transcript_exon	Exon 13 of 18	ENSP00000385496.2
	SPAG16	ENST00000406979.6	TSL:1	n.*1084A>C		3_prime_UTR	Exon 13 of 18	ENSP00000385496.2

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

GnomAD2 exomes AF: 0.390 AC: 97955 AN: 251166 AF XY: 0.393

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 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

African (AFR) AF: 0.216 AC: 7226 AN: 33476

American (AMR) AF: 0.425 AC: 18987 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7966 AN: 26124

East Asian (EAS) AF: 0.488 AC: 19357 AN: 39688

South Asian (SAS) AF: 0.465 AC: 40114 AN: 86246

European-Finnish (FIN) AF: 0.399 AC: 21299 AN: 53400

Middle Eastern (MID) AF: 0.348 AC: 2004 AN: 5756

European-Non Finnish (NFE) AF: 0.377 AC: 419183 AN: 1111670

Other (OTH) AF: 0.367 AC: 22169 AN: 60386

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

African (AFR) AF: 0.228 AC: 9468 AN: 41454

American (AMR) AF: 0.399 AC: 6092 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2347 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2292 AN: 4804

European-Finnish (FIN) AF: 0.394 AC: 4152 AN: 10542

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25404 AN: 67948

Other (OTH) AF: 0.334 AC: 704 AN: 2110

Alfa AF: 0.364 Hom.: 38607

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 v4.9

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
MetaRNN	Benign	0.00084	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.67
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	6.7	N
REVEL	Benign	0.089
Sift	Benign	1.0	T
Sift4G	Benign	1.0	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2042791; hg19: chr2-214727221; COSMIC: COSV59079144;