rs61752199

Variant names:

• chr2-213490087-G-A
• rs61752199
• NM_024532.5:c.1067G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000331683.10(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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (24 hom., cov: 32)
  • Exomes 𝑓: 0.017 (311 hom.)
• Consequence: SPAG16 ENST00000331683.10 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043849945).
• BP6: Variant 2-213490087-G-A is Benign according to our data. Variant chr2-213490087-G-A is described in ClinVar as Benign. ClinVar VariationId is 3341511.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000331683.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	NM_024532.5	MANE Select	c.1067G>A	p.Ser356Asn	missense	Exon 10 of 16	NP_078808.3
	SPAG16	NR_047659.2		n.1262G>A		non_coding_transcript_exon	Exon 12 of 18
	SPAG16	NR_047660.2		n.968G>A		non_coding_transcript_exon	Exon 9 of 15

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.1067G>A	p.Ser356Asn	missense	Exon 10 of 16	ENSP00000332592.5
	SPAG16	ENST00000406979.6	TSL:1	n.*1068G>A		non_coding_transcript_exon	Exon 12 of 18	ENSP00000385496.2
	SPAG16	ENST00000406979.6	TSL:1	n.*1068G>A		3_prime_UTR	Exon 12 of 18	ENSP00000385496.2

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

GnomAD2 exomes AF: 0.0179 AC: 3892 AN: 217896 AF XY: 0.0194

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 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

African (AFR) AF: 0.00834 AC: 257 AN: 30812

American (AMR) AF: 0.00903 AC: 325 AN: 35998

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 1520 AN: 24610

East Asian (EAS) AF: 0.00132 AC: 50 AN: 37976

South Asian (SAS) AF: 0.0417 AC: 3275 AN: 78570

European-Finnish (FIN) AF: 0.0118 AC: 624 AN: 52728

Middle Eastern (MID) AF: 0.0283 AC: 157 AN: 5544

European-Non Finnish (NFE) AF: 0.0153 AC: 16812 AN: 1096308

Other (OTH) AF: 0.0197 AC: 1153 AN: 58500

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

African (AFR) AF: 0.00782 AC: 325 AN: 41556

American (AMR) AF: 0.0142 AC: 217 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4826

European-Finnish (FIN) AF: 0.0131 AC: 139 AN: 10584

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1094 AN: 68000

Other (OTH) AF: 0.0157 AC: 33 AN: 2108

Alfa AF: 0.0158 Hom.: 55

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.87	P
Vest4		0.081
MPC		0.15
ClinPred		0.014	T
GERP RS		5.0
PromoterAI		0.018	Neutral
Varity_R		0.60
gMVP		0.25
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61752199; hg19: chr2-214354811;