Variant chr21-46161521-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142854.2(SPATC1L):c.881A>T(p.Asn294Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,609,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029695868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATC1L	NM_001142854.2 linkuse as main transcript	c.881A>T	p.Asn294Ile	missense_variant	5/5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 linkuse as main transcript	c.419A>T	p.Asn140Ile	missense_variant	4/4		NP_115637.3
SPATC1L	XM_005261188.6 linkuse as main transcript	c.881A>T	p.Asn294Ile	missense_variant	5/5		XP_005261245.1
SPATC1L	XM_011529756.3 linkuse as main transcript	c.539A>T	p.Asn180Ile	missense_variant	3/3		XP_011528058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6 linkuse as main transcript	c.881A>T	p.Asn294Ile	missense_variant	5/5	2	NM_001142854.2	ENSP00000291672	P1	Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.419A>T	p.Asn140Ile	missense_variant	4/4	1		ENSP00000333869		Q9H0A9-2

Frequencies

GnomAD3 genomes

AF:

0.000303

AC:

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

239140

Hom.:

AF XY:

0.0000612

AC XY:

AN XY:

130670

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.0000884

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

151

AN:

1457974

Hom.:

Cov.:

AF XY:

0.0000910

AC XY:

AN XY:

725136

show subpopulations

Gnomad4 AFR exome

AF:

0.000987

Gnomad4 AMR exome

AF:

0.000135

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:

0.0000945

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000309

AC:

AN:

151872

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.000989

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.000374

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000997

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 17, 2023

The c.881A>T (p.N294I) alteration is located in exon 5 (coding exon 4) of the SPATC1L gene. This alteration results from a A to T substitution at nucleotide position 881, causing the asparagine (N) at amino acid position 294 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

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.022

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

.;N

MutationTaster

Benign

0.55

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.023

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.047

.;B

Vest4

0.32

MVP

0.32

MPC

0.50

ClinPred

0.033

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.59

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