chr21-46179262-T-C

Variant names:

• chr21-46179262-T-C
• rs8133866
• NM_001142854.2:c.193+3362A>G

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+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
• Publications: 14 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: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPATC1L	NM_001142854.2	c.193+3362A>G		intron_variant	Intron 2 of 4	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5	c.-270+5094A>G		intron_variant	Intron 1 of 3		NP_115637.3
SPATC1L	XM_005261188.6	c.193+3362A>G		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+3362A>G		intron_variant	Intron 2 of 4	2	NM_001142854.2	ENSP00000291672.5
SPATC1L	ENST00000330205.10	c.-270+5094A>G		intron_variant	Intron 1 of 3	1		ENSP00000333869.6

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

African (AFR) AF: 0.564 AC: 23226 AN: 41204

American (AMR) AF: 0.188 AC: 2857 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3464

East Asian (EAS) AF: 0.00236 AC: 12 AN: 5086

South Asian (SAS) AF: 0.157 AC: 747 AN: 4744

European-Finnish (FIN) AF: 0.149 AC: 1556 AN: 10460

Middle Eastern (MID) AF: 0.271 AC: 78 AN: 288

European-Non Finnish (NFE) AF: 0.236 AC: 15992 AN: 67714

Other (OTH) AF: 0.291 AC: 609 AN: 2090

Alfa AF: 0.258 Hom.: 5579

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
PhyloP100		-0.93
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: rs8133866; hg19: chr21-47599176;