rs8133866

Positions:

• chr21-46179262-T-C
• chrNT_187626.1-40631-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142854.2(SPATC1L):​c.193+3362A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,162 control chromosomes in the GnomAD database, including 9,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9224 hom., cov: 31)
• Consequence: SPATC1L NM_001142854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATC1L	NM_001142854.2	c.193+3362A>G		intron_variant		ENST00000291672.6
SPATC1L	NM_032261.5	c.-270+5094A>G		intron_variant
SPATC1L	XM_005261188.6	c.193+3362A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATC1L	ENST00000291672.6	c.193+3362A>G		intron_variant		2	NM_001142854.2	P1
SPATC1L	ENST00000330205.10	c.-270+5094A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46085 AN: 151044 Hom.: 9203 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.00235

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 46148 AN: 151162 Hom.: 9224 Cov.: 31 AF XY: 0.294 AC XY: 21711 AN XY: 73828

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.00236

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.291

Alfa AF: 0.243 Hom.: 3653

Bravo AF: 0.320

Asia WGS AF: 0.124 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.31

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: rs8133866; hg19: chr21-47599176;