rs8133205

Variant names:

• chr21-46179366-C-T
• rs8133205
• NM_001142854.2:c.193+3258G>A

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+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
• Publications: 16 publications found

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]

SPATC1L Gene-Disease associations (from GenCC):

• hearing loss disorder

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142854.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATC1L	NM_001142854.2	MANE Select	c.193+3258G>A		intron	N/A	NP_001136326.1	Q9H0A9-1
	SPATC1L	NM_032261.5		c.-270+4990G>A		intron	N/A	NP_115637.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATC1L	ENST00000291672.6	TSL:2 MANE Select	c.193+3258G>A		intron	N/A	ENSP00000291672.5	Q9H0A9-1
	SPATC1L	ENST00000330205.10	TSL:1	c.-270+4990G>A		intron	N/A	ENSP00000333869.6	Q9H0A9-2
	SPATC1L	ENST00000872418.1		c.193+3258G>A		intron	N/A	ENSP00000542477.1

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

African (AFR) AF: 0.414 AC: 17143 AN: 41390

American (AMR) AF: 0.136 AC: 2081 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0470 AC: 226 AN: 4804

European-Finnish (FIN) AF: 0.128 AC: 1353 AN: 10552

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12307 AN: 67996

Other (OTH) AF: 0.203 AC: 428 AN: 2110

Alfa AF: 0.194 Hom.: 1718

Bravo AF: 0.235

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.82
PhyloP100		0.21
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

Other links and lift over

dbSNP: rs8133205; hg19: chr21-47599280;