rs9637184

Positions:

• chr21-44571155-A-G

Variant summary

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

The NM_144991.3(TSPEAR):​c.83-3150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,254 control chromosomes in the GnomAD database, including 4,491 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 0.23 (4491 hom., cov: 33)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPEAR	NM_144991.3	c.83-3150T>C		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2	c.-122-3150T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPEAR	ENST00000323084.9	c.83-3150T>C		intron_variant		1	NM_144991.3	P1
TSPEAR	ENST00000397916.1	n.37+2625T>C		intron_variant, non_coding_transcript_variant		1
TSPEAR	ENST00000642437.1	c.*28-3150T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35259 AN: 152136 Hom.: 4494 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.232 AC: 35278 AN: 152254 Hom.: 4491 Cov.: 33 AF XY: 0.236 AC XY: 17548 AN XY: 74438

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.209

Alfa AF: 0.222 Hom.: 817

Bravo AF: 0.243

Asia WGS AF: 0.353 AC: 1223 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	0.62
DANN	Benign	0.48

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: rs9637184; hg19: chr21-45991038;