rs14378

chr21-46161509-C-GchrNT_187626.1-20945-C-Gchr21-46161509-C-TchrNT_187626.1-20945-C-Tchr21-46161509-C-AchrNT_187626.1-20945-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142854.2(SPATC1L):c.893G>C(p.Ser298Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. S298N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPATC1L NM_001142854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10965639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATC1L	NM_001142854.2	c.893G>C	p.Ser298Thr	missense_variant	5/5	ENST00000291672.6
SPATC1L	NM_032261.5	c.431G>C	p.Ser144Thr	missense_variant	4/4
SPATC1L	XM_005261188.6	c.893G>C	p.Ser298Thr	missense_variant	5/5
SPATC1L	XM_011529756.3	c.551G>C	p.Ser184Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATC1L	ENST00000291672.6	c.893G>C	p.Ser298Thr	missense_variant	5/5	2	NM_001142854.2	P1
SPATC1L	ENST00000330205.10	c.431G>C	p.Ser144Thr	missense_variant	4/4	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000420 AC: 1 AN: 238008 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad SAS 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.: 33

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000832 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Benign	0.95
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.91	P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.026
Sift	Benign	0.22	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.19	.;B
Vest4		0.31
MutPred		0.16		.;Loss of disorder (P = 0.0557);
MVP		0.31
MPC		0.32
ClinPred		0.26	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs14378; hg19: chr21-47581423;