rs7074847

Variant names:

• chr10-22386928-A-G
• rs7074847
• NM_012443.4:c.647A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012443.4(SPAG6):​c.647A>G​(p.Gln216Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0384 in 1,613,474 control chromosomes in the GnomAD database, including 10,837 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.

• Frequency:
  • Genomes: 𝑓 0.16 (5538 hom., cov: 32)
  • Exomes 𝑓: 0.026 (5299 hom.)
• Consequence: SPAG6 NM_012443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18
• Publications: 13 publications found

Genes affected

SPAG6 (HGNC:11215): (sperm associated antigen 6) The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from an infertile man. This protein localizes to the tail of permeabilized human sperm and contains eight contiguous armadillo repeats, a motif known to mediate protein-protein interactions. Studies in mice suggest that this protein is involved in sperm flagellar motility and maintenance of the structural integrity of mature sperm. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ENSG00000233451 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.201863E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012443.4. 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
	SPAG6	NM_012443.4	MANE Select	c.647A>G	p.Gln216Arg	missense	Exon 5 of 11	NP_036575.1
	SPAG6	NM_001253854.2		c.572A>G	p.Gln191Arg	missense	Exon 8 of 14	NP_001240783.1
	SPAG6	NM_001253855.2		c.581A>G	p.Gln194Arg	missense	Exon 4 of 11	NP_001240784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG6	ENST00000376624.8	TSL:1 MANE Select	c.647A>G	p.Gln216Arg	missense	Exon 5 of 11	ENSP00000365811.3
	SPAG6	ENST00000376603.6	TSL:1	c.581A>G	p.Gln194Arg	missense	Exon 4 of 11	ENSP00000365788.3
	SPAG6	ENST00000313311.10	TSL:1	c.647A>G	p.Gln216Arg	missense	Exon 5 of 10	ENSP00000323599.6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23700 AN: 152062 Hom.: 5502 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0768

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.118

GnomAD2 exomes AF: 0.0505 AC: 12679 AN: 250868 AF XY: 0.0404

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.0406

Gnomad ASJ exome AF: 0.0456

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00619

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0407

GnomAD4 exome AF: 0.0261 AC: 38171 AN: 1461294 Hom.: 5299 Cov.: 32 AF XY: 0.0242 AC XY: 17615 AN XY: 726942

African (AFR) AF: 0.534 AC: 17857 AN: 33416

American (AMR) AF: 0.0457 AC: 2043 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0437 AC: 1141 AN: 26128

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39690

South Asian (SAS) AF: 0.00914 AC: 788 AN: 86248

European-Finnish (FIN) AF: 0.00652 AC: 348 AN: 53392

Middle Eastern (MID) AF: 0.0827 AC: 472 AN: 5706

European-Non Finnish (NFE) AF: 0.0112 AC: 12464 AN: 1111662

Other (OTH) AF: 0.0506 AC: 3052 AN: 60366

GnomAD4 genome AF: 0.156 AC: 23787 AN: 152180 Hom.: 5538 Cov.: 32 AF XY: 0.150 AC XY: 11190 AN XY: 74440

African (AFR) AF: 0.510 AC: 21114 AN: 41434

American (AMR) AF: 0.0767 AC: 1173 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4830

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10626

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 950 AN: 68026

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.0567 Hom.: 5493

Bravo AF: 0.179

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.509 AC: 2243

ESP6500EA AF: 0.0160 AC: 138

ExAC AF: 0.0595 AC: 7224

Asia WGS AF: 0.0510 AC: 179 AN: 3478

EpiCase AF: 0.0190

EpiControl AF: 0.0176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.65
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.00062	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.19
Sift	Benign	0.43	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.31
MPC		0.30
ClinPred		0.020	T
GERP RS		4.5
Varity_R		0.36
gMVP		0.48
Mutation Taster		=90/10	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: rs7074847; hg19: chr10-22675857;