13-24223426-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001166271.3(SPATA13):c.497C>T(p.Pro166Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,551,048 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P166A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (6 hom.)
• Consequence: SPATA13 NM_001166271.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.206

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074641705).
• BP6: Variant 13-24223426-C-T is Benign according to our data. Variant chr13-24223426-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA13	NM_001166271.3	c.497C>T	p.Pro166Leu	missense_variant	2/13	ENST00000382108.8
SPATA13	NM_001286792.2	c.683C>T	p.Pro228Leu	missense_variant	4/15
SPATA13	NM_153023.4	c.-222-26051C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA13	ENST00000382108.8	c.497C>T	p.Pro166Leu	missense_variant	2/13	5	NM_001166271.3
SPATA13	ENST00000424834.6	c.497C>T	p.Pro166Leu	missense_variant	4/15	1
SPATA13	ENST00000382095.8	c.-222-26051C>T		intron_variant		2
SPATA13	ENST00000466831.2	n.819C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00175 AC: 272 AN: 155272 Hom.: 0 AF XY: 0.00188 AC XY: 155 AN XY: 82494

Gnomad AFR exome AF: 0.000509

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000460

Gnomad SAS exome AF: 0.00110

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00291

Gnomad OTH exome AF: 0.00252

GnomAD4 exome AF: 0.00252 AC: 3528 AN: 1398722 Hom.: 6 Cov.: 29 AF XY: 0.00244 AC XY: 1685 AN XY: 689922

Gnomad4 AFR exome AF: 0.000506

Gnomad4 AMR exome AF: 0.00137

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000196

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.00109

Gnomad4 NFE exome AF: 0.00296

Gnomad4 OTH exome AF: 0.00198

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00144 AC XY: 107 AN XY: 74488

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00230 Hom.: 2

Bravo AF: 0.00158

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00675 AC: 26

ExAC AF: 0.00138 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SPATA13-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 10, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	5.1
Dann	Benign	0.91
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.043	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.0075	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.17	T;T
Vest4		0.088
MVP		0.12
MPC		0.30
ClinPred		0.015	T
GERP RS		-1.3
gMVP		0.10

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: rs150850951; hg19: chr13-24797564;