21-44509026-AGTCCCCAGGCCATTCTTTCCACAGGAAG-A

Position:

• chr21-44509026-AGTCCCCAGGCCATTCTTTCCACAGGAAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_144991.3(TSPEAR):​c.1754+145_1754+172del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,451,302 control chromosomes in the GnomAD database, including 115 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (82 hom.)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.945

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]

TSPEAR-AS1 (HGNC:1271): (TSPEAR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-44509026-AGTCCCCAGGCCATTCTTTCCACAGGAAG-A is Benign according to our data. Variant chr21-44509026-AGTCCCCAGGCCATTCTTTCCACAGGAAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0173 (2616/150892) while in subpopulation AFR AF= 0.0277 (1119/40386). AF 95% confidence interval is 0.0264. There are 33 homozygotes in gnomad4. There are 1208 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPEAR	NM_144991.3	c.1754+145_1754+172del		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR-AS1	NR_103707.1	n.1214+138_1215-158del		intron_variant, non_coding_transcript_variant
TSPEAR	NM_001272037.2	c.1550+145_1550+172del		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPEAR	ENST00000323084.9	c.1754+145_1754+172del		intron_variant		1	NM_144991.3	ENSP00000321987	P1
TSPEAR	ENST00000397916.1	n.1710-143_1710-116del		intron_variant, non_coding_transcript_variant		1
TSPEAR-AS1	ENST00000451035.2	n.769+138_770-158del		intron_variant, non_coding_transcript_variant		5
TSPEAR	ENST00000642437.1	c.*1699+145_*1699+172del		intron_variant, NMD_transcript_variant				ENSP00000496535

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2606 AN: 150788 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00670

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0155

GnomAD4 exome AF: 0.00671 AC: 8729 AN: 1300410 Hom.: 82 AF XY: 0.00690 AC XY: 4427 AN XY: 641858

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.00901

Gnomad4 ASJ exome AF: 0.00447

Gnomad4 EAS exome AF: 0.000806

Gnomad4 SAS exome AF: 0.00541

Gnomad4 FIN exome AF: 0.00600

Gnomad4 NFE exome AF: 0.00669

Gnomad4 OTH exome AF: 0.00819

GnomAD4 genome AF: 0.0173 AC: 2616 AN: 150892 Hom.: 33 Cov.: 32 AF XY: 0.0164 AC XY: 1208 AN XY: 73762

Gnomad4 AFR AF: 0.0277

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.00670

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0153

Alfa AF: 0.0152 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879970586; hg19: chr21-45928909;