21-46161921-C-T

Position:

chr21-46161921-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.691G>A(p.Glu231Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 1,605,954 control chromosomes in the GnomAD database, including 5,497 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 ( 393 hom., cov: 33)

Exomes 𝑓: 0.077 ( 5104 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.15

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=0.0014095306).

BP6

Variant 21-46161921-C-T is Benign according to our data. Variant chr21-46161921-C-T is described in ClinVar as [Benign]. Clinvar id is 403469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPATC1L	NM_001142854.2 linkuse as main transcript	c.691G>A	p.Glu231Lys	missense_variant	4/5	ENST00000291672.6
SPATC1L	NM_032261.5 linkuse as main transcript	c.229G>A	p.Glu77Lys	missense_variant	3/4
SPATC1L	XM_005261188.6 linkuse as main transcript	c.691G>A	p.Glu231Lys	missense_variant	4/5
SPATC1L	XM_011529756.3 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATC1L	ENST00000291672.6 linkuse as main transcript	c.691G>A	p.Glu231Lys	missense_variant	4/5	2	NM_001142854.2	P1	Q9H0A9-1
SPATC1L	ENST00000330205.10 linkuse as main transcript	c.229G>A	p.Glu77Lys	missense_variant	3/4	1			Q9H0A9-2

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9280

AN:

152028

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0639

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0454

Gnomad FIN

AF:

0.0995

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0846

Gnomad OTH

AF:

0.0651

GnomAD3 exomes

AF:

0.0648

AC:

15271

AN:

235782

Hom.:

633

AF XY:

0.0668

AC XY:

8654

AN XY:

129576

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.0866

Gnomad EAS exome

AF:

0.0151

Gnomad SAS exome

AF:

0.0507

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.0874

Gnomad OTH exome

AF:

0.0751

GnomAD4 exome

AF:

0.0772

AC:

112172

AN:

1453808

Hom.:

5104

Cov.:

AF XY:

0.0767

AC XY:

55522

AN XY:

723546

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.0379

Gnomad4 ASJ exome

AF:

0.0845

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.0542

Gnomad4 FIN exome

AF:

0.0908

Gnomad4 NFE exome

AF:

0.0845

Gnomad4 OTH exome

AF:

0.0691

GnomAD4 genome

AF:

0.0610

AC:

9277

AN:

152146

Hom.:

393

Cov.:

AF XY:

0.0611

AC XY:

4548

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.0638

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0450

Gnomad4 FIN

AF:

0.0995

Gnomad4 NFE

AF:

0.0846

Gnomad4 OTH

AF:

0.0644

Alfa

AF:

0.0784

Hom.:

247

Bravo

AF:

0.0562

TwinsUK

AF:

0.0887

AC:

329

ALSPAC

AF:

0.0817

AC:

315

ESP6500AA

AF:

0.0160

AC:

ESP6500EA

AF:

0.0869

AC:

746

ExAC

AF:

0.0658

AC:

7909

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0856

EpiControl

AF:

0.0876

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 11, 2019

This variant is associated with the following publications: (PMID: 30177775, 28339009) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.062

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.77

N;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.0

.;B

Vest4

0.14

MPC

0.19

ClinPred

0.018

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.43

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