rs61752199

chr2-213490087-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024532.5(SPAG16):c.1067G>A(p.Ser356Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,573,270 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (24 hom., cov: 32)
  • Exomes 𝑓: 0.017 (311 hom.)
• Consequence: SPAG16 NM_024532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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=0.0043849945).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0146 (2215/152224) while in subpopulation SAS AF= 0.0381 (184/4826). AF 95% confidence interval is 0.0336. There are 24 homozygotes in gnomad4. There are 1086 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG16	NM_024532.5	c.1067G>A	p.Ser356Asn	missense_variant	10/16	ENST00000331683.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG16	ENST00000331683.10	c.1067G>A	p.Ser356Asn	missense_variant	10/16	1	NM_024532.5	P1
SPAG16	ENST00000406979.6	c.*1068G>A		3_prime_UTR_variant, NMD_transcript_variant	12/18	1
SPAG16	ENST00000451561.1	c.125G>A	p.Ser42Asn	missense_variant	1/6	3
SPAG16	ENST00000452556.5	c.*633G>A		3_prime_UTR_variant, NMD_transcript_variant	8/14	2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2210 AN: 152106 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00777

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0179 AC: 3892 AN: 217896 Hom.: 67 AF XY: 0.0194 AC XY: 2302 AN XY: 118516

Gnomad AFR exome AF: 0.00678

Gnomad AMR exome AF: 0.00898

Gnomad ASJ exome AF: 0.0628

Gnomad EAS exome AF: 0.00199

Gnomad SAS exome AF: 0.0425

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0157

Gnomad OTH exome AF: 0.0233

GnomAD4 exome AF: 0.0170 AC: 24173 AN: 1421046 Hom.: 311 Cov.: 30 AF XY: 0.0178 AC XY: 12584 AN XY: 706484

Gnomad4 AFR exome AF: 0.00834

Gnomad4 AMR exome AF: 0.00903

Gnomad4 ASJ exome AF: 0.0618

Gnomad4 EAS exome AF: 0.00132

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0153

Gnomad4 OTH exome AF: 0.0197

GnomAD4 genome AF: 0.0146 AC: 2215 AN: 152224 Hom.: 24 Cov.: 32 AF XY: 0.0146 AC XY: 1086 AN XY: 74430

Gnomad4 AFR AF: 0.00782

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0164 Hom.: 48

Bravo AF: 0.0132

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0143 AC: 55

ESP6500AA AF: 0.00750 AC: 33

ESP6500EA AF: 0.0179 AC: 154

ExAC AF: 0.0184 AC: 2228

Asia WGS AF: 0.0350 AC: 121 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0044	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.87	P;.
Vest4		0.081
MPC		0.15
ClinPred		0.014	T
GERP RS		5.0
Varity_R		0.60
gMVP		0.25

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: rs61752199; hg19: chr2-214354811;