Variant 21-46161925-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001142854.2(SPATC1L):c.687G>C(p.Lys229Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.584

Variant links:

Genes affected

SPATC1L (HGNC:1298): (spermatogenesis and centriole associated 1 like) Enables identical protein binding activity. Predicted to act upstream of or within several processes, including actin polymerization or depolymerization; positive regulation of cAMP-dependent protein kinase activity; and positive regulation of protein kinase A signaling. Predicted to be located in sperm connecting piece. Predicted to be active in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

SPATC1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATC1L	NM_001142854.2 linkuse as main transcript	c.687G>C	p.Lys229Asn	missense_variant	4/5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 linkuse as main transcript	c.225G>C	p.Lys75Asn	missense_variant	3/4		NP_115637.3
SPATC1L	XM_005261188.6 linkuse as main transcript	c.687G>C	p.Lys229Asn	missense_variant	4/5		XP_005261245.1	Q9H0A9-1
SPATC1L	XM_011529756.3 linkuse as main transcript	c.345G>C	p.Lys115Asn	missense_variant	2/3		XP_011528058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6 linkuse as main transcript	c.687G>C	p.Lys229Asn	missense_variant	4/5	2	NM_001142854.2	ENSP00000291672.5		Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.225G>C	p.Lys75Asn	missense_variant	3/4	1		ENSP00000333869.6		Q9H0A9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000211

AC:

AN:

237016

Hom.:

AF XY:

0.00000769

AC XY:

AN XY:

130120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454694

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.687G>C (p.K229N) alteration is located in exon 4 (coding exon 3) of the SPATC1L gene. This alteration results from a G to C substitution at nucleotide position 687, causing the lysine (K) at amino acid position 229 to be replaced by an asparagine (N). 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

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.3

D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.75

MutPred

0.33

.;Loss of methylation at K229 (P = 0.0011);

MVP

0.41

MPC

0.77

ClinPred

0.85

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.82

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over