21-46162035-C-T

Position:

chr21-46162035-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.577G>A(p.Ala193Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,589,382 control chromosomes in the GnomAD database, including 5,339 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 392 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4947 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.920

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=0.0013727844).

BP6

Variant 21-46162035-C-T is Benign according to our data. Variant chr21-46162035-C-T is described in ClinVar as [Benign]. Clinvar id is 403470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATC1L	NM_001142854.2 linkuse as main transcript	c.577G>A	p.Ala193Thr	missense_variant	4/5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 linkuse as main transcript	c.115G>A	p.Ala39Thr	missense_variant	3/4		NP_115637.3
SPATC1L	XM_005261188.6 linkuse as main transcript	c.577G>A	p.Ala193Thr	missense_variant	4/5		XP_005261245.1	Q9H0A9-1
SPATC1L	XM_011529756.3 linkuse as main transcript	c.235G>A	p.Ala79Thr	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.577G>A	p.Ala193Thr	missense_variant	4/5	2	NM_001142854.2	ENSP00000291672.5		Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.115G>A	p.Ala39Thr	missense_variant	3/4	1		ENSP00000333869.6		Q9H0A9-2

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

9242

AN:

152058

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0636

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0840

Gnomad OTH

AF:

0.0649

GnomAD3 exomes

AF:

0.0650

AC:

13135

AN:

201988

Hom.:

530

AF XY:

0.0669

AC XY:

7407

AN XY:

110796

show subpopulations

Gnomad AFR exome

AF:

0.0145

Gnomad AMR exome

AF:

0.0363

Gnomad ASJ exome

AF:

0.0864

Gnomad EAS exome

AF:

0.0155

Gnomad SAS exome

AF:

0.0521

Gnomad FIN exome

AF:

0.0916

Gnomad NFE exome

AF:

0.0884

Gnomad OTH exome

AF:

0.0723

GnomAD4 exome

AF:

0.0766

AC:

110119

AN:

1437208

Hom.:

4947

Cov.:

AF XY:

0.0762

AC XY:

54379

AN XY:

713526

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.0844

Gnomad4 EAS exome

AF:

0.0122

Gnomad4 SAS exome

AF:

0.0545

Gnomad4 FIN exome

AF:

0.0922

Gnomad4 NFE exome

AF:

0.0836

Gnomad4 OTH exome

AF:

0.0685

GnomAD4 genome

AF:

0.0607

AC:

9239

AN:

152174

Hom.:

392

Cov.:

AF XY:

0.0610

AC XY:

4542

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.0635

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0449

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.0840

Gnomad4 OTH

AF:

0.0643

Alfa

AF:

0.0754

Hom.:

504

Bravo

AF:

0.0558

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0815

AC:

314

ESP6500AA

AF:

0.0162

AC:

ESP6500EA

AF:

0.0851

AC:

729

ExAC

AF:

0.0600

AC:

7149

Asia WGS

AF:

0.0200

AC:

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

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0060

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.14

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.015

Sift

Benign

0.15

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.16

.;B

Vest4

0.16

MPC

0.19

ClinPred

0.0039

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.18

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