chr16-89657833-T-C

Position:

• chr16-89657833-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000301031.8(SPATA33):​c.32T>C​(p.Phe11Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: SPATA33 ENST00000301031.8 missense, splice_region
• Scores: Splicing: ADA: 0.00004900
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.310

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03056404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA33	NM_001271907.2			upstream_gene_variant		ENST00000579310.6	NP_001258836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA33	ENST00000579310.6			upstream_gene_variant		2	NM_001271907.2	ENSP00000462996	P2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151654 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151654 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74044

Gnomad4 AFR AF: 0.0000726

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.32T>C (p.F11S) alteration is located in exon 1 (coding exon 1) of the SPATA33 gene. This alteration results from a T to C substitution at nucleotide position 32, causing the phenylalanine (F) at amino acid position 11 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.2
DANN	Benign	0.36
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.031	T
MutationTaster	Benign	1.0	N;N
Sift4G	Benign	1.0	T
MVP		0.030
ClinPred		0.13	T
GERP RS		-0.070

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.0
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: rs983465542; hg19: chr16-89724241;