chr16-89669376-G-C

Position:

• chr16-89669376-G-C

Variant summary

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

The NM_001271907.2(SPATA33):​c.302G>C​(p.Ser101Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA33 NM_001271907.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

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 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=0.14629692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA33	NM_001271907.2	c.302G>C	p.Ser101Thr	missense_variant	3/3	ENST00000579310.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA33	ENST00000579310.6	c.302G>C	p.Ser101Thr	missense_variant	3/3	2	NM_001271907.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 06, 2023

The c.299G>C (p.S100T) alteration is located in exon 3 (coding exon 3) of the SPATA33 gene. This alteration results from a G to C substitution at nucleotide position 299, causing the serine (S) at amino acid position 100 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.57
DEOGEN2	Benign	0.032	T;.;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.47	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.;.
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.6	N;.;.;.
REVEL	Benign	0.10
Sift	Benign	0.10	T;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;.;.;.
Vest4		0.061
MutPred		0.17		Loss of phosphorylation at S100 (P = 0.0857);.;.;.;
MVP		0.27
MPC		0.047
ClinPred		0.76	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-89735784;