16-89658340-A-G

Position:

• chr16-89658340-A-G

Variant summary

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

The NM_001271907.2(SPATA33):​c.130A>G​(p.Arg44Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA33 NM_001271907.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.369

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]

SPATA33 (HGNC:):

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=0.05969739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA33	NM_001271907.2	c.130A>G	p.Arg44Gly	missense_variant	2/3	ENST00000579310.6	NP_001258836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA33	ENST00000579310.6	c.130A>G	p.Arg44Gly	missense_variant	2/3	2	NM_001271907.2	ENSP00000462996.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jul 15, 2024

The c.127A>G (p.R43G) alteration is located in exon 2 (coding exon 2) of the SPATA33 gene. This alteration results from a A to G substitution at nucleotide position 127, causing the arginine (R) at amino acid position 43 to be replaced by a glycine (G). 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	0.083
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.3
DANN	Benign	0.75
DEOGEN2	Benign	0.042	T;.;.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.47	T;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.060	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.;.;.
PROVEAN	Uncertain	-2.6	D;.;.;.;.
REVEL	Benign	0.051
Sift	Benign	0.14	T;.;.;.;.
Sift4G	Uncertain	0.014	D;D;D;D;D
Polyphen		0.0020	B;.;.;.;.
Vest4		0.037
MutPred		0.14		Loss of solvent accessibility (P = 0.0329);.;.;.;.;
MVP		0.12
MPC		0.014
ClinPred		0.030	T
GERP RS		-0.87
Varity_R		0.083
gMVP		0.015

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: chr16-89724748;