rs14378

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S298G) has been classified as Uncertain significance.

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

Publications

10 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: AR, AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, 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=0.0012110174).

BP6

Variant 21-46161509-C-T is Benign according to our data. Variant chr21-46161509-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142854.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATC1L	NM_001142854.2	MANE Select	c.893G>A	p.Ser298Asn	missense	Exon 5 of 5	NP_001136326.1	Q9H0A9-1
	SPATC1L	NM_032261.5		c.431G>A	p.Ser144Asn	missense	Exon 4 of 4	NP_115637.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATC1L	ENST00000291672.6	TSL:2 MANE Select	c.893G>A	p.Ser298Asn	missense	Exon 5 of 5	ENSP00000291672.5	Q9H0A9-1
SPATC1L	ENST00000330205.10	TSL:1	c.431G>A	p.Ser144Asn	missense	Exon 4 of 4	ENSP00000333869.6	Q9H0A9-2
SPATC1L	ENST00000872418.1		c.893G>A	p.Ser298Asn	missense	Exon 4 of 4	ENSP00000542477.1

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

GnomAD2 exomes

AF:

0.0891

AC:

21199

AN:

238008

AF XY:

0.0913

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 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

African (AFR)

AF:

0.142

AC:

4739

AN:

33376

American (AMR)

AF:

0.0527

AC:

2337

AN:

44384

Ashkenazi Jewish (ASJ)

AF:

0.0966

AC:

2512

AN:

26006

East Asian (EAS)

AF:

0.0146

AC:

578

AN:

39534

South Asian (SAS)

AF:

0.117

AC:

10095

AN:

85922

European-Finnish (FIN)

AF:

0.0965

AC:

4970

AN:

51518

Middle Eastern (MID)

AF:

0.0824

AC:

474

AN:

5750

European-Non Finnish (NFE)

AF:

0.0918

AC:

101794

AN:

1109100

Other (OTH)

AF:

0.0912

AC:

5480

AN:

60066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

7501

15002

22504

30005

37506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3730

7460

11190

14920

18650

<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:

0.105

AC:

15928

AN:

152060

Hom.:

970

Cov.:

AF XY:

0.105

AC XY:

7807

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.142

AC:

5894

AN:

41494

American (AMR)

AF:

0.0875

AC:

1339

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0988

AC:

343

AN:

3472

East Asian (EAS)

AF:

0.0175

AC:

AN:

5156

South Asian (SAS)

AF:

0.119

AC:

575

AN:

4832

European-Finnish (FIN)

AF:

0.101

AC:

1066

AN:

10580

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0916

AC:

6224

AN:

67922

Other (OTH)

AF:

0.116

AC:

244

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

728

1455

2183

2910

3638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0961

Hom.:

1106

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.42

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.0

PhyloP100

1.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.26

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.070

MPC

0.16

ClinPred

0.0090

GERP RS

3.3

Varity_R

0.059

gMVP

0.29

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over