13-24223324-A-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.395A>T(p.Asn132Ile) 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. 13/18 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)
• Consequence: SPATA13 NM_001166271.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.631

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=0.12052107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA13	NM_001166271.3	c.395A>T	p.Asn132Ile	missense_variant	2/13	ENST00000382108.8
SPATA13	NM_001286792.2	c.581A>T	p.Asn194Ile	missense_variant	4/15
SPATA13	NM_153023.4	c.-222-26153A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA13	ENST00000382108.8	c.395A>T	p.Asn132Ile	missense_variant	2/13	5	NM_001166271.3
SPATA13	ENST00000424834.6	c.395A>T	p.Asn132Ile	missense_variant	4/15	1
SPATA13	ENST00000382095.8	c.-222-26153A>T		intron_variant		2
SPATA13	ENST00000466831.2	n.717A>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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 07, 2022

The c.395A>T (p.N132I) alteration is located in exon 2 (coding exon 1) of the SPATA13 gene. This alteration results from a A to T substitution at nucleotide position 395, causing the asparagine (N) at amino acid position 132 to be replaced by an isoleucine (I). 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	-0.15	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	6.2
Dann	Benign	0.97
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.16	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.77	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
Sift4G	Uncertain	0.010	D;D
Vest4		0.15
MutPred		0.36		Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);
MVP		0.17
MPC		0.53
ClinPred		0.74	D
GERP RS		-3.4
gMVP		0.19

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: chr13-24797462;