Genetic Variant NM_001142854.2:c.875G>T (chr21-46161527-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001142854.2(SPATC1L):c.875G>T(p.Arg292Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R292H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30202773).

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.875G>T	p.Arg292Leu	missense	Exon 5 of 5	NP_001136326.1	Q9H0A9-1
	SPATC1L	NM_032261.5		c.413G>T	p.Arg138Leu	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.875G>T	p.Arg292Leu	missense	Exon 5 of 5	ENSP00000291672.5	Q9H0A9-1
SPATC1L	ENST00000330205.10	TSL:1	c.413G>T	p.Arg138Leu	missense	Exon 4 of 4	ENSP00000333869.6	Q9H0A9-2
SPATC1L	ENST00000872418.1		c.875G>T	p.Arg292Leu	missense	Exon 4 of 4	ENSP00000542477.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000417

AC:

AN:

239750

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000665

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.72

M_CAP

Benign

0.043

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.6

PhyloP100

2.5

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

REVEL

Benign

0.069

Sift

Benign

0.29

Sift4G

Benign

0.19

Polyphen

0.97

Vest4

0.51

MutPred

0.26

Loss of methylation at R292 (P = 0.0442)

MVP

0.41

MPC

0.71

ClinPred

0.45

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.54

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over