13-24223429-G-T

Variant summary

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

The NM_001166271.3(SPATA13):c.500G>T(p.Gly167Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: SPATA13 NM_001166271.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

Genes affected

SPATA13 (HGNC:23222): (spermatogenesis associated 13) Enables guanyl-nucleotide exchange factor activity and identical protein binding activity. Involved in cell migration; plasma membrane bounded cell projection assembly; and regulation of cell migration. Located in several cellular components, including filopodium; lamellipodium; and ruffle membrane. [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=0.20358366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA13	NM_001166271.3	c.500G>T	p.Gly167Val	missense_variant	2/13	ENST00000382108.8
SPATA13	NM_001286792.2	c.686G>T	p.Gly229Val	missense_variant	4/15
SPATA13	NM_153023.4	c.-222-26048G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA13	ENST00000382108.8	c.500G>T	p.Gly167Val	missense_variant	2/13	5	NM_001166271.3
SPATA13	ENST00000424834.6	c.500G>T	p.Gly167Val	missense_variant	4/15	1
SPATA13	ENST00000382095.8	c.-222-26048G>T		intron_variant		2
SPATA13	ENST00000466831.2	n.822G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 33

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

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: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

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

Oct 05, 2023

The c.500G>T (p.G167V) alteration is located in exon 2 (coding exon 1) of the SPATA13 gene. This alteration results from a G to T substitution at nucleotide position 500, causing the glycine (G) at amino acid position 167 to be replaced by a valine (V). 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
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	13
Dann	Benign	0.93
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
Sift4G	Uncertain	0.010	D;D
Vest4		0.29
MutPred		0.29		Gain of catalytic residue at G167 (P = 0.0017);Gain of catalytic residue at G167 (P = 0.0017);
MVP		0.30
MPC		0.82
ClinPred		0.95	D
GERP RS		0.92
gMVP		0.27

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

Other links and lift over

dbSNP: rs1363778088; hg19: chr13-24797567;