13-24223508-C-A

Position:

• chr13-24223508-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001166271.3(SPATA13):​c.579C>A​(p.Phe193Leu) 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. 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: 0.323

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31640655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA13	NM_001166271.3	c.579C>A	p.Phe193Leu	missense_variant	2/13	ENST00000382108.8
SPATA13	NM_001286792.2	c.765C>A	p.Phe255Leu	missense_variant	4/15
SPATA13	NM_153023.4	c.-222-25969C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA13	ENST00000382108.8	c.579C>A	p.Phe193Leu	missense_variant	2/13	5	NM_001166271.3
SPATA13	ENST00000424834.6	c.579C>A	p.Phe193Leu	missense_variant	4/15	1
SPATA13	ENST00000382095.8	c.-222-25969C>A		intron_variant		2
SPATA13	ENST00000466831.2	n.901C>A		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

Mar 01, 2023

The c.579C>A (p.F193L) alteration is located in exon 2 (coding exon 1) of the SPATA13 gene. This alteration results from a C to A substitution at nucleotide position 579, causing the phenylalanine (F) at amino acid position 193 to be replaced by a leucine (L). 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	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.90	D
Sift4G	Benign	0.18	T;T
Vest4		0.43
MutPred		0.33		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.64
MPC		1.1
ClinPred		0.99	D
GERP RS		3.3
gMVP		0.099

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: chr13-24797646;