21-46161509-C-T

Position:

chr21-46161509-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142854.2(SPATC1L):c.893G>A(p.Ser298Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 1,607,716 control chromosomes in the GnomAD database, including 7,828 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 970 hom., cov: 31)

Exomes 𝑓: 0.091 ( 6858 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.10

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012110174).

BP6

Variant 21-46161509-C-T is Benign according to our data. Variant chr21-46161509-C-T is described in ClinVar as [Benign]. Clinvar id is 403468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATC1L	NM_001142854.2 linkuse as main transcript	c.893G>A	p.Ser298Asn	missense_variant	5/5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 linkuse as main transcript	c.431G>A	p.Ser144Asn	missense_variant	4/4		NP_115637.3
SPATC1L	XM_005261188.6 linkuse as main transcript	c.893G>A	p.Ser298Asn	missense_variant	5/5		XP_005261245.1
SPATC1L	XM_011529756.3 linkuse as main transcript	c.551G>A	p.Ser184Asn	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.893G>A	p.Ser298Asn	missense_variant	5/5	2	NM_001142854.2	ENSP00000291672	P1	Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.431G>A	p.Ser144Asn	missense_variant	4/4	1		ENSP00000333869		Q9H0A9-2

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15879

AN:

151942

Hom.:

962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0877

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.0176

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0916

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0891

AC:

21199

AN:

238008

Hom.:

1112

AF XY:

0.0913

AC XY:

11869

AN XY:

130014

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0497

Gnomad ASJ exome

AF:

0.0991

Gnomad EAS exome

AF:

0.0191

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.0963

Gnomad NFE exome

AF:

0.0952

Gnomad OTH exome

AF:

0.0878

GnomAD4 exome

AF:

0.0914

AC:

132979

AN:

1455656

Hom.:

6858

Cov.:

AF XY:

0.0920

AC XY:

66568

AN XY:

723542

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.0527

Gnomad4 ASJ exome

AF:

0.0966

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.0965

Gnomad4 NFE exome

AF:

0.0918

Gnomad4 OTH exome

AF:

0.0912

GnomAD4 genome

AF:

0.105

AC:

15928

AN:

152060

Hom.:

970

Cov.:

AF XY:

0.105

AC XY:

7807

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0875

Gnomad4 ASJ

AF:

0.0988

Gnomad4 EAS

AF:

0.0175

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0916

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.0917

Hom.:

648

Bravo

AF:

0.103

TwinsUK

AF:

0.0963

AC:

357

ALSPAC

AF:

0.0913

AC:

352

ESP6500AA

AF:

0.136

AC:

597

ESP6500EA

AF:

0.0943

AC:

809

ExAC

AF:

0.0918

AC:

11030

Asia WGS

AF:

0.104

AC:

359

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30177775) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0054

.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.42

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.0

.;N

MutationTaster

Benign

0.89

P;P

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.070

MPC

0.16

ClinPred

0.0090

GERP RS

3.3

Varity_R

0.059

gMVP

0.29

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