rs12627324

Positions:

• chr21-44568543-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.83-538C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,020 control chromosomes in the GnomAD database, including 4,412 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 (4412 hom., cov: 33)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPEAR	NM_144991.3	c.83-538C>A		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-538C>A		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPEAR	ENST00000323084.9	c.83-538C>A		intron_variant		1	NM_144991.3	ENSP00000321987	P1
TSPEAR	ENST00000397916.1	n.38-538C>A		intron_variant, non_coding_transcript_variant		1
TSPEAR	ENST00000642437.1	c.*28-538C>A		intron_variant, NMD_transcript_variant				ENSP00000496535

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34860 AN: 151904 Hom.: 4414 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.229 AC: 34879 AN: 152020 Hom.: 4412 Cov.: 33 AF XY: 0.234 AC XY: 17357 AN XY: 74316

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.210

Alfa AF: 0.198 Hom.: 1589

Bravo AF: 0.240

Asia WGS AF: 0.350 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.81

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: rs12627324; hg19: chr21-45988426;