3-172913671-A-G

Position:

• chr3-172913671-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_031955.6(SPATA16):​c.1577T>C​(p.Met526Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,612,806 control chromosomes in the GnomAD database, including 458 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (29 hom., cov: 32)
  • Exomes 𝑓: 0.022 (429 hom.)
• Consequence: SPATA16 NM_031955.6 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031369925).
• BP6: Variant 3-172913671-A-G is Benign according to our data. Variant chr3-172913671-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 901937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.019 (2890/152282) while in subpopulation NFE AF= 0.0245 (1666/68024). AF 95% confidence interval is 0.0235. There are 29 homozygotes in gnomad4. There are 1423 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA16	NM_031955.6	c.1577T>C	p.Met526Thr	missense_variant	10/11	ENST00000351008.4	NP_114161.3
SPATA16	XM_006713778.4	c.1577T>C	p.Met526Thr	missense_variant	10/11		XP_006713841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA16	ENST00000351008.4	c.1577T>C	p.Met526Thr	missense_variant	10/11	1	NM_031955.6	ENSP00000341765.3
SPATA16	ENST00000652082.1	n.*141T>C		non_coding_transcript_exon_variant	7/8			ENSP00000498213.1
SPATA16	ENST00000652082.1	n.*141T>C		3_prime_UTR_variant	7/8			ENSP00000498213.1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2884 AN: 152164 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0190 AC: 4778 AN: 251090 Hom.: 66 AF XY: 0.0192 AC XY: 2612 AN XY: 135726

Gnomad AFR exome AF: 0.0114

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.0244

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0234

GnomAD4 exome AF: 0.0216 AC: 31605 AN: 1460524 Hom.: 429 Cov.: 30 AF XY: 0.0215 AC XY: 15623 AN XY: 726634

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0114

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0232

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0190 AC: 2890 AN: 152282 Hom.: 29 Cov.: 32 AF XY: 0.0191 AC XY: 1423 AN XY: 74454

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.0231 Hom.: 84

Bravo AF: 0.0183

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0202 AC: 78

ESP6500AA AF: 0.00931 AC: 41

ESP6500EA AF: 0.0230 AC: 198

ExAC AF: 0.0199 AC: 2414

Asia WGS AF: 0.00520 AC: 20 AN: 3478

EpiCase AF: 0.0265

EpiControl AF: 0.0270

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Globozoospermia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.49
DEOGEN2	Benign	0.00075	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.052	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.069
MPC		0.14
ClinPred		0.0022	T
GERP RS		4.5
Varity_R		0.047
gMVP		0.069

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: rs62622782; hg19: chr3-172631461;