rs2838659

Positions:

• chr21-44708323-G-A
• chr21-44708323-G-T

Variant summary

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

The NM_144991.3(TSPEAR):​c.82+3110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,838 control chromosomes in the GnomAD database, including 6,197 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 0.28 (6197 hom., cov: 31)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPEAR	NM_144991.3	c.82+3110C>T		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-185+3110C>T		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPEAR	ENST00000323084.9	c.82+3110C>T		intron_variant		1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000642437.1	n.82+3110C>T		intron_variant				ENSP00000496535.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42392 AN: 151720 Hom.: 6184 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.279 AC: 42432 AN: 151838 Hom.: 6197 Cov.: 31 AF XY: 0.285 AC XY: 21149 AN XY: 74186

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.279

Alfa AF: 0.244 Hom.: 7834

Bravo AF: 0.278

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.83

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: rs2838659; hg19: chr21-46128238;