dbSNP rs772927581: SPATC1L:p.Glu276Lys (chr21-46161576-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_001142854.2(SPATC1L):c.826G>A(p.Glu276Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,458,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70

Publications

1 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: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

BS2

High AC in GnomAdExome4 at 17 AD gene.

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.826G>A	p.Glu276Lys	missense	Exon 5 of 5	NP_001136326.1	Q9H0A9-1
	SPATC1L	NM_032261.5		c.364G>A	p.Glu122Lys	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.826G>A	p.Glu276Lys	missense	Exon 5 of 5	ENSP00000291672.5	Q9H0A9-1
SPATC1L	ENST00000330205.10	TSL:1	c.364G>A	p.Glu122Lys	missense	Exon 4 of 4	ENSP00000333869.6	Q9H0A9-2
SPATC1L	ENST00000872418.1		c.826G>A	p.Glu276Lys	missense	Exon 4 of 4	ENSP00000542477.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000417

AC:

AN:

239890

AF XY:

0.00000763

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1458034

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39628

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1110918

Other (OTH)

AF:

0.00

AC:

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000829

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.070

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.92

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.1

PhyloP100

2.7

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.74

MutPred

0.73

Gain of methylation at E276 (P = 0.0024)

MVP

0.52

MPC

0.64

ClinPred

0.98

GERP RS

4.4

Varity_R

0.86

gMVP

0.86

Mutation Taster

=91/9

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over