Genetic Variant SPATC1L:p.Ser234Pro (chr21-46161702-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142854.2(SPATC1L):c.700T>C(p.Ser234Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPATC1L
NM_001142854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATC1L	NM_001142854.2 link	c.700T>C	p.Ser234Pro	missense_variant	Exon 5 of 5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5 link	c.238T>C	p.Ser80Pro	missense_variant	Exon 4 of 4		NP_115637.3
SPATC1L	XM_005261188.6 link	c.700T>C	p.Ser234Pro	missense_variant	Exon 5 of 5		XP_005261245.1	Q9H0A9-1
SPATC1L	XM_011529756.3 link	c.358T>C	p.Ser120Pro	missense_variant	Exon 3 of 3		XP_011528058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6 link	c.700T>C	p.Ser234Pro	missense_variant	Exon 5 of 5	2	NM_001142854.2	ENSP00000291672.5		Q9H0A9-1
SPATC1L	ENST00000330205.10 link	c.238T>C	p.Ser80Pro	missense_variant	Exon 4 of 4	1		ENSP00000333869.6		Q9H0A9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710306

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.700T>C (p.S234P) alteration is located in exon 5 (coding exon 4) of the SPATC1L gene. This alteration results from a T to C substitution at nucleotide position 700, causing the serine (S) at amino acid position 234 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.082

FATHMM_MKL

Benign

0.57

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.95

.;L

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.071

T;T

Polyphen

0.0040

.;B

Vest4

0.63

MVP

0.32

MPC

0.23

ClinPred

0.83

GERP RS

4.2

Varity_R

0.58

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over