chr16-89657905-C-G

Position:

• chr16-89657905-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000564238.2(SPATA33):​c.35C>G​(p.Ala12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,517,082 control chromosomes in the GnomAD database, including 4,523 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (656 hom., cov: 32)
  • Exomes 𝑓: 0.017 (3867 hom.)
• Consequence: SPATA33 ENST00000564238.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.371

Genes affected

SPATA33 (HGNC:26463): (spermatogenesis associated 33) Predicted to act upstream of or within cellular protein localization; fertilization; and flagellated sperm motility. Predicted to be located in sperm mitochondrial sheath. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 16-89657905-C-G is Benign according to our data. Variant chr16-89657905-C-G is described in ClinVar as [Benign]. Clinvar id is 1235871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA33	NM_001271907.2	c.-7C>G		5_prime_UTR_variant	1/3	ENST00000579310.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA33	ENST00000579310.6	c.-7C>G		5_prime_UTR_variant	1/3	2	NM_001271907.2	P2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3624 AN: 151964 Hom.: 654 Cov.: 32

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0415 AC: 4660 AN: 112224 Hom.: 986 AF XY: 0.0402 AC XY: 2514 AN XY: 62592

Gnomad AFR exome AF: 0.00323

Gnomad AMR exome AF: 0.00282

Gnomad ASJ exome AF: 0.00442

Gnomad EAS exome AF: 0.509

Gnomad SAS exome AF: 0.0179

Gnomad FIN exome AF: 0.0326

Gnomad NFE exome AF: 0.00270

Gnomad OTH exome AF: 0.0240

GnomAD4 exome AF: 0.0168 AC: 22970 AN: 1365010 Hom.: 3867 Cov.: 32 AF XY: 0.0170 AC XY: 11478 AN XY: 673638

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00461

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.0204

Gnomad4 FIN exome AF: 0.0288

Gnomad4 NFE exome AF: 0.00259

Gnomad4 OTH exome AF: 0.0359

GnomAD4 genome AF: 0.0238 AC: 3624 AN: 152072 Hom.: 656 Cov.: 32 AF XY: 0.0269 AC XY: 1997 AN XY: 74320

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.00392

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00547 Hom.: 8

Bravo AF: 0.0241

Asia WGS AF: 0.210 AC: 725 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.1
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11545432; hg19: chr16-89724313;