Variant 21-46161594-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001142854.2(SPATC1L):c.808G>T(p.Val270Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,610,254 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 157 hom., cov: 31)

Exomes 𝑓: 0.0026 ( 157 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.464

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021375418).

BP6

Variant 21-46161594-C-A is Benign according to our data. Variant chr21-46161594-C-A is described in ClinVar as [Benign]. Clinvar id is 769141.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPATC1L	NM_001142854.2 linkuse as main transcript	c.808G>T	p.Val270Leu	missense_variant	5/5	ENST00000291672.6
SPATC1L	NM_032261.5 linkuse as main transcript	c.346G>T	p.Val116Leu	missense_variant	4/4
SPATC1L	XM_005261188.6 linkuse as main transcript	c.808G>T	p.Val270Leu	missense_variant	5/5
SPATC1L	XM_011529756.3 linkuse as main transcript	c.466G>T	p.Val156Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATC1L	ENST00000291672.6 linkuse as main transcript	c.808G>T	p.Val270Leu	missense_variant	5/5	2	NM_001142854.2	P1	Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.346G>T	p.Val116Leu	missense_variant	4/4	1			Q9H0A9-2

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3726

AN:

152086

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0843

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00628

AC:

1503

AN:

239406

Hom.:

AF XY:

0.00466

AC XY:

610

AN XY:

130866

show subpopulations

Gnomad AFR exome

AF:

0.0878

Gnomad AMR exome

AF:

0.00450

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000215

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00256

AC:

3734

AN:

1458050

Hom.:

157

Cov.:

AF XY:

0.00221

AC XY:

1605

AN XY:

725180

show subpopulations

Gnomad4 AFR exome

AF:

0.0881

Gnomad4 AMR exome

AF:

0.00527

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.0246

AC:

3743

AN:

152204

Hom.:

157

Cov.:

AF XY:

0.0238

AC XY:

1775

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0845

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.0287

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0924

AC:

406

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00788

AC:

949

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 29, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.077

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.51

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.94

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.038

Sift

Benign

0.19

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.39

.;B

Vest4

0.12

MutPred

0.48

.;Gain of catalytic residue at V270 (P = 0.0179);

MVP

0.27

MPC

0.20

ClinPred

0.011

GERP RS

4.3

Varity_R

0.15

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