chr21-46182235-G-A

Variant names:

• chr21-46182235-G-A
• rs8134519
• NM_001142854.2:c.193+389C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142854.2(SPATC1L):​c.193+389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,960 control chromosomes in the GnomAD database, including 2,748 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 0.17 (2748 hom., cov: 33)
• Consequence: SPATC1L NM_001142854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATC1L	NM_001142854.2	c.193+389C>T		intron_variant	Intron 2 of 4	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5	c.-270+2121C>T		intron_variant	Intron 1 of 3		NP_115637.3
SPATC1L	XM_005261188.6	c.193+389C>T		intron_variant	Intron 2 of 4		XP_005261245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATC1L	ENST00000291672.6	c.193+389C>T		intron_variant	Intron 2 of 4	2	NM_001142854.2	ENSP00000291672.5
SPATC1L	ENST00000330205.10	c.-270+2121C>T		intron_variant	Intron 1 of 3	1		ENSP00000333869.6

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26285 AN: 151840 Hom.: 2747 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0804

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.173 AC: 26303 AN: 151960 Hom.: 2748 Cov.: 33 AF XY: 0.166 AC XY: 12344 AN XY: 74330

African (AFR) AF: 0.294 AC: 12149 AN: 41388

American (AMR) AF: 0.116 AC: 1775 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3468

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5150

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4826

European-Finnish (FIN) AF: 0.102 AC: 1079 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9914 AN: 67920

Other (OTH) AF: 0.172 AC: 362 AN: 2110

Alfa AF: 0.156 Hom.: 835

Bravo AF: 0.183

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.79
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs8134519; hg19: chr21-47602149;