3-172913722-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031955.6(SPATA16):c.1526C>T(p.Ala509Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,613,078 control chromosomes in the GnomAD database, including 455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (29 hom., cov: 32)
  • Exomes 𝑓: 0.022 (426 hom.)
• Consequence: SPATA16 NM_031955.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.52

Genes affected

SPATA16 (HGNC:29935): (spermatogenesis associated 16) This gene encodes a testis-specific protein that belongs to the tetratricopeptide repeat-like superfamily. The encoded protein localizes to the Golgi apparatus and may play a role in spermatogenesis. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008070976).
• BP6: Variant 3-172913722-G-A is Benign according to our data. Variant chr3-172913722-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 344204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2857/152178) while in subpopulation NFE AF= 0.0245 (1667/68008). AF 95% confidence interval is 0.0235. There are 29 homozygotes in gnomad4. There are 1406 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA16	NM_031955.6	c.1526C>T	p.Ala509Val	missense_variant	10/11	ENST00000351008.4
SPATA16	XM_006713778.4	c.1526C>T	p.Ala509Val	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA16	ENST00000351008.4	c.1526C>T	p.Ala509Val	missense_variant	10/11	1	NM_031955.6	P1
SPATA16	ENST00000652082.1	c.*90C>T		3_prime_UTR_variant, NMD_transcript_variant	7/8

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2855 AN: 152060 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0253

GnomAD3 exomes AF: 0.0190 AC: 4776 AN: 251004 Hom.: 66 AF XY: 0.0193 AC XY: 2613 AN XY: 135656

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.0341

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.0253

Gnomad OTH exome AF: 0.0238

GnomAD4 exome AF: 0.0217 AC: 31739 AN: 1460900 Hom.: 426 Cov.: 30 AF XY: 0.0216 AC XY: 15681 AN XY: 726752

Gnomad4 AFR exome AF: 0.00995

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0234

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.0188 AC: 2857 AN: 152178 Hom.: 29 Cov.: 32 AF XY: 0.0189 AC XY: 1406 AN XY: 74382

Gnomad4 AFR AF: 0.00991

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0266

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0225 Hom.: 32

Bravo AF: 0.0179

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0202 AC: 78

ESP6500AA AF: 0.00840 AC: 37

ESP6500EA AF: 0.0230 AC: 198

ExAC AF: 0.0198 AC: 2408

Asia WGS AF: 0.00491 AC: 19 AN: 3478

EpiCase AF: 0.0265

EpiControl AF: 0.0273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Globozoospermia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.26
MPC		0.39
ClinPred		0.022	T
GERP RS		5.5
Varity_R		0.39
gMVP		0.44

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: rs115095786; hg19: chr3-172631512;