rs6518275

Variant names:

• chr21-46179904-C-T
• rs6518275
• NM_001142854.2:c.193+2720G>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+2720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,300 control chromosomes in the GnomAD database, including 1,139 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 0.069 (1139 hom., cov: 33)
• Consequence: SPATC1L NM_001142854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATC1L	NM_001142854.2	c.193+2720G>A		intron_variant	Intron 2 of 4	ENST00000291672.6	NP_001136326.1
SPATC1L	NM_032261.5	c.-270+4452G>A		intron_variant	Intron 1 of 3		NP_115637.3
SPATC1L	XM_005261188.6	c.193+2720G>A		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+2720G>A		intron_variant	Intron 2 of 4	2	NM_001142854.2	ENSP00000291672.5
SPATC1L	ENST00000330205.10	c.-270+4452G>A		intron_variant	Intron 1 of 3	1		ENSP00000333869.6

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10468 AN: 152182 Hom.: 1139 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0688 AC: 10475 AN: 152300 Hom.: 1139 Cov.: 33 AF XY: 0.0659 AC XY: 4906 AN XY: 74482

African (AFR) AF: 0.235 AC: 9754 AN: 41532

American (AMR) AF: 0.0311 AC: 476 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00144 AC: 98 AN: 68032

Other (OTH) AF: 0.0553 AC: 117 AN: 2114

Alfa AF: 0.0366 Hom.: 198

Bravo AF: 0.0790

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.71
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: rs6518275; hg19: chr21-47599818;