rs447735

Variant names:

• chr16-89667941-T-C
• rs447735
• NM_001271907.2:c.212-1345T>C

Variant summary

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

The NM_001271907.2(SPATA33):​c.212-1345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,204 control chromosomes in the GnomAD database, including 10,126 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (10113 hom., cov: 33)
  • Exomes 𝑓: 0.46 (13 hom.)
• Consequence: SPATA33 NM_001271907.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 23 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA33	NM_001271907.2	c.212-1345T>C		intron_variant	Intron 2 of 2	ENST00000579310.6	NP_001258836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA33	ENST00000579310.6	c.212-1345T>C		intron_variant	Intron 2 of 2	2	NM_001271907.2	ENSP00000462996.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49849 AN: 151990 Hom.: 10112 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.458 AC: 44 AN: 96 Hom.: 13 AF XY: 0.500 AC XY: 37 AN XY: 74

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.512 AC: 41 AN: 80

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.328 AC: 49852 AN: 152108 Hom.: 10113 Cov.: 33 AF XY: 0.322 AC XY: 23964 AN XY: 74332

African (AFR) AF: 0.125 AC: 5171 AN: 41532

American (AMR) AF: 0.366 AC: 5595 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1900 AN: 3472

East Asian (EAS) AF: 0.0205 AC: 106 AN: 5180

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4824

European-Finnish (FIN) AF: 0.375 AC: 3961 AN: 10566

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30399 AN: 67946

Other (OTH) AF: 0.408 AC: 861 AN: 2112

Alfa AF: 0.411 Hom.: 7987

Bravo AF: 0.320

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.55
PhyloP100		0.29
Mutation Taster		=100/0	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: rs447735; hg19: chr16-89734349;