3-172916419-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031955.6(SPATA16):c.1401G>T(p.Gln467His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: SPATA16 NM_031955.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0880

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106258154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA16	NM_031955.6	c.1401G>T	p.Gln467His	missense_variant	9/11	ENST00000351008.4
SPATA16	XM_006713778.4	c.1401G>T	p.Gln467His	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA16	ENST00000351008.4	c.1401G>T	p.Gln467His	missense_variant	9/11	1	NM_031955.6	P1
SPATA16	ENST00000652082.1	c.610G>T	p.Ala204Ser	missense_variant, NMD_transcript_variant	6/8

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000155 AC: 39 AN: 251272 Hom.: 0 AF XY: 0.000199 AC XY: 27 AN XY: 135784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000304 AC: 444 AN: 1461636 Hom.: 0 Cov.: 33 AF XY: 0.000305 AC XY: 222 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000367

Gnomad4 OTH exome AF: 0.000315

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74300

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000240 Hom.: 0

Bravo AF: 0.000249

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Globozoospermia Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	17
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.047
Eigen_PC	Benign	-0.0078
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.087
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	D
Polyphen		0.76	P
Vest4		0.20
MutPred		0.14		Loss of disorder (P = 0.0812);
MVP		0.41
MPC		0.25
ClinPred		0.079	T
GERP RS		4.1
Varity_R		0.16
gMVP		0.40

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: rs143774140; hg19: chr3-172634209;