chr21-46161921-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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:3

Conservation

PhyloP100: 1.15

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

hearing loss disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SPATC1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SPATC1L	NM_001142854.2 link	c.691G>A	p.Glu231Lys	missense_variant	Exon 4 of 5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 link	c.229G>A	p.Glu77Lys	missense_variant	Exon 3 of 4		NP_115637.3
SPATC1L	XM_005261188.6 link	c.691G>A	p.Glu231Lys	missense_variant	Exon 4 of 5		XP_005261245.1	Q9H0A9-1
SPATC1L	XM_011529756.3 link	c.349G>A	p.Glu117Lys	missense_variant	Exon 2 of 3		XP_011528058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6 link	c.691G>A	p.Glu231Lys	missense_variant	Exon 4 of 5	2	NM_001142854.2	ENSP00000291672.5		Q9H0A9-1
SPATC1L	ENST00000330205.10 link	c.229G>A	p.Glu77Lys	missense_variant	Exon 3 of 4	1		ENSP00000333869.6		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

GnomAD2 exomes

AF:

0.0648

AC:

15271

AN:

235782

AF XY:

0.0668

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 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

African (AFR)

AF:

0.0143

AC:

478

AN:

33444

American (AMR)

AF:

0.0379

AC:

1693

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.0845

AC:

2202

AN:

26052

East Asian (EAS)

AF:

0.0123

AC:

489

AN:

39660

South Asian (SAS)

AF:

0.0542

AC:

4667

AN:

86084

European-Finnish (FIN)

AF:

0.0908

AC:

4255

AN:

46884

Middle Eastern (MID)

AF:

0.0627

AC:

359

AN:

5722

European-Non Finnish (NFE)

AF:

0.0845

AC:

93870

AN:

1111154

Other (OTH)

AF:

0.0691

AC:

4159

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6456

12911

19367

25822

32278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3344

6688

10032

13376

16720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0610

AC:

9277

AN:

152146

Hom.:

393

Cov.:

AF XY:

0.0611

AC XY:

4548

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0169

AC:

703

AN:

41560

American (AMR)

AF:

0.0638

AC:

976

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0859

AC:

298

AN:

3470

East Asian (EAS)

AF:

0.0114

AC:

AN:

5166

South Asian (SAS)

AF:

0.0450

AC:

217

AN:

4822

European-Finnish (FIN)

AF:

0.0995

AC:

1055

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0846

AC:

5747

AN:

67912

Other (OTH)

AF:

0.0644

AC:

136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

415

831

1246

1662

2077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0750

Hom.:

307

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

0.040

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0028

.;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.062

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

.;N

PhyloP100

1.2

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over