Variant chr21-46161623-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142854.2(SPATC1L):c.779G>T(p.Arg260Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,610,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.815

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0714933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATC1L	NM_001142854.2 linkuse as main transcript	c.779G>T	p.Arg260Leu	missense_variant	5/5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 linkuse as main transcript	c.317G>T	p.Arg106Leu	missense_variant	4/4		NP_115637.3
SPATC1L	XM_005261188.6 linkuse as main transcript	c.779G>T	p.Arg260Leu	missense_variant	5/5		XP_005261245.1	Q9H0A9-1
SPATC1L	XM_011529756.3 linkuse as main transcript	c.437G>T	p.Arg146Leu	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.779G>T	p.Arg260Leu	missense_variant	5/5	2	NM_001142854.2	ENSP00000291672.5		Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.317G>T	p.Arg106Leu	missense_variant	4/4	1		ENSP00000333869.6		Q9H0A9-2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000420

AC:

AN:

237828

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130328

show subpopulations

Gnomad AFR exome

AF:

0.000673

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1458154

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

725242

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.000217

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000581

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

Jul 14, 2021

The c.779G>T (p.R260L) alteration is located in exon 5 (coding exon 4) of the SPATC1L gene. This alteration results from a G to T substitution at nucleotide position 779, causing the arginine (R) at amino acid position 260 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

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

.;T

Eigen

Benign

-0.035

Eigen_PC

Benign

-0.080

FATHMM_MKL

Benign

0.23

M_CAP

Benign

0.049

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.8

.;L

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.87

.;P

Vest4

0.34

MVP

0.38

MPC

0.36

ClinPred

0.26

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.75

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