chr21-46161539-C-G

Variant names:

• chr21-46161539-C-G
• rs771485808
• NM_001142854.2:c.863G>C

Variant summary

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

The NM_001142854.2(SPATC1L):​c.863G>C​(p.Arg288Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,334 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPATC1L NM_001142854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548

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 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	c.863G>C	p.Arg288Pro	missense_variant	Exon 5 of 5	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5	c.401G>C	p.Arg134Pro	missense_variant	Exon 4 of 4		NP_115637.3
SPATC1L	XM_005261188.6	c.863G>C	p.Arg288Pro	missense_variant	Exon 5 of 5		XP_005261245.1
SPATC1L	XM_011529756.3	c.521G>C	p.Arg174Pro	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	c.863G>C	p.Arg288Pro	missense_variant	Exon 5 of 5	2	NM_001142854.2	ENSP00000291672.5
SPATC1L	ENST00000330205.10	c.401G>C	p.Arg134Pro	missense_variant	Exon 4 of 4	1		ENSP00000333869.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000416 AC: 1 AN: 240370 Hom.: 0 AF XY: 0.00000761 AC XY: 1 AN XY: 131348

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000933

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458334 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725376

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000830 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.71	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.0	.;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	.;D
Vest4		0.46
MutPred		0.60		.;Gain of catalytic residue at R288 (P = 0.0506);
MVP		0.57
MPC		0.86
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.86
gMVP		0.83

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: rs771485808; hg19: chr21-47581453;