13-24223452-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001166271.3(SPATA13):c.523C>T(p.Pro175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000787 in 1,398,166 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: SPATA13 NM_001166271.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.142

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052550375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA13	NM_001166271.3	c.523C>T	p.Pro175Ser	missense_variant	2/13	ENST00000382108.8
SPATA13	NM_001286792.2	c.709C>T	p.Pro237Ser	missense_variant	4/15
SPATA13	NM_153023.4	c.-222-26025C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA13	ENST00000382108.8	c.523C>T	p.Pro175Ser	missense_variant	2/13	5	NM_001166271.3
SPATA13	ENST00000424834.6	c.523C>T	p.Pro175Ser	missense_variant	4/15	1
SPATA13	ENST00000382095.8	c.-222-26025C>T		intron_variant		2
SPATA13	ENST00000466831.2	n.845C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000787 AC: 11 AN: 1398166 Hom.: 0 Cov.: 29 AF XY: 0.00000580 AC XY: 4 AN XY: 689708

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Sep 16, 2021

The c.523C>T (p.P175S) alteration is located in exon 2 (coding exon 1) of the SPATA13 gene. This alteration results from a C to T substitution at nucleotide position 523, causing the proline (P) at amino acid position 175 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
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	0.076
Dann	Benign	0.37
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.049	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.25	T;T
Vest4		0.064
MutPred		0.17		Gain of catalytic residue at C170 (P = 0.011);Gain of catalytic residue at C170 (P = 0.011);
MVP		0.43
MPC		0.30
ClinPred		0.023	T
GERP RS		-4.2
gMVP		0.11

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: chr13-24797590;