2-213489990-C-A

Position:

• chr2-213489990-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000331683.10(SPAG16):​c.970C>A​(p.Pro324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 1,606,586 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.025 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (155 hom.)
• Consequence: SPAG16 ENST00000331683.10 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.706

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023835301).
• BP6: Variant 2-213489990-C-A is Benign according to our data. Variant chr2-213489990-C-A is described in ClinVar as [Benign]. Clinvar id is 788696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG16	NM_024532.5	c.970C>A	p.Pro324Thr	missense_variant	10/16	ENST00000331683.10	NP_078808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10	c.970C>A	p.Pro324Thr	missense_variant	10/16	1	NM_024532.5	ENSP00000332592	P1
SPAG16	ENST00000406979.6	c.*971C>A		3_prime_UTR_variant, NMD_transcript_variant	12/18	1		ENSP00000385496
SPAG16	ENST00000451561.1	c.28C>A	p.Pro10Thr	missense_variant	1/6	3		ENSP00000416600
SPAG16	ENST00000452556.5	c.*536C>A		3_prime_UTR_variant, NMD_transcript_variant	8/14	2		ENSP00000398926

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3788 AN: 152062 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00626 AC: 1532 AN: 244590 Hom.: 59 AF XY: 0.00467 AC XY: 618 AN XY: 132454

Gnomad AFR exome AF: 0.0813

Gnomad AMR exome AF: 0.00569

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000242

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000482

Gnomad OTH exome AF: 0.00338

GnomAD4 exome AF: 0.00267 AC: 3886 AN: 1454406 Hom.: 155 Cov.: 29 AF XY: 0.00233 AC XY: 1684 AN XY: 723340

Gnomad4 AFR exome AF: 0.0853

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000296

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000264

Gnomad4 OTH exome AF: 0.00724

GnomAD4 genome AF: 0.0250 AC: 3803 AN: 152180 Hom.: 156 Cov.: 32 AF XY: 0.0243 AC XY: 1810 AN XY: 74402

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00448 Hom.: 26

Bravo AF: 0.0283

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0756 AC: 333

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00764 AC: 927

Asia WGS AF: 0.00752 AC: 27 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.16
DEOGEN2	Benign	0.073	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.52	T;T
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.022
Sift	Benign	0.61	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.44	B;.
Vest4		0.23
MVP		0.58
MPC		0.024
ClinPred		0.020	T
GERP RS		2.9
Varity_R		0.062
gMVP		0.23

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: rs10167688; hg19: chr2-214354714;