Variant 16-89669414-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001271907.2(SPATA33):c.340C>G(p.Arg114Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SPATA33
NM_001271907.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.224

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.15443441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA33	NM_001271907.2 linkuse as main transcript	c.340C>G	p.Arg114Gly	missense_variant	3/3	ENST00000579310.6	NP_001258836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA33	ENST00000579310.6 linkuse as main transcript	c.340C>G	p.Arg114Gly	missense_variant	3/3	2	NM_001271907.2	ENSP00000462996	P2	Q96N06-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.337C>G (p.R113G) alteration is located in exon 3 (coding exon 3) of the SPATA33 gene. This alteration results from a C to G substitution at nucleotide position 337, causing the arginine (R) at amino acid position 113 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

0.33

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.065

T;.;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.54

T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;.;.;.

MutationTaster

Benign

1.0

N;N

PROVEAN

Pathogenic

-4.8

D;.;.;.

REVEL

Benign

0.072

Sift

Uncertain

0.0070

D;.;.;.

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.97

D;.;.;.

Vest4

0.12

MutPred

0.29

Loss of sheet (P = 0.0181);.;.;.;

MVP

0.32

MPC

0.047

ClinPred

0.94

GERP RS

0.73

Varity_R

0.32

gMVP

0.072

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over