rs8133205

Positions:

• chr21-46179366-C-T
• chrNT_187626.1-40735-C-T

Variant summary

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

The NM_001142854.2(SPATC1L):​c.193+3258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,960 control chromosomes in the GnomAD database, including 5,016 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 0.22 (5016 hom., cov: 32)
• Consequence: SPATC1L NM_001142854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATC1L	NM_001142854.2	c.193+3258G>A		intron_variant		ENST00000291672.6
SPATC1L	NM_032261.5	c.-270+4990G>A		intron_variant
SPATC1L	XM_005261188.6	c.193+3258G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATC1L	ENST00000291672.6	c.193+3258G>A		intron_variant		2	NM_001142854.2	P1
SPATC1L	ENST00000330205.10	c.-270+4990G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34050 AN: 151842 Hom.: 5013 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.224 AC: 34076 AN: 151960 Hom.: 5016 Cov.: 32 AF XY: 0.215 AC XY: 15955 AN XY: 74256

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.203

Alfa AF: 0.203 Hom.: 743

Bravo AF: 0.235

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.82

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: rs8133205; hg19: chr21-47599280;