21-44572248-T-C

Position:

• chr21-44572248-T-C

Variant summary

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

The NM_144991.3(TSPEAR):​c.83-4243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,676 control chromosomes in the GnomAD database, including 36,898 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 0.69 (36898 hom., cov: 31)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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 (Cadd=2.636).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPEAR	NM_144991.3	c.83-4243A>G		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2	c.-122-4243A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPEAR	ENST00000323084.9	c.83-4243A>G		intron_variant		1	NM_144991.3	P1
TSPEAR	ENST00000397916.1	n.37+1532A>G		intron_variant, non_coding_transcript_variant		1
TSPEAR	ENST00000642437.1	c.*28-4243A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104087 AN: 151558 Hom.: 36877 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.687 AC: 104156 AN: 151676 Hom.: 36898 Cov.: 31 AF XY: 0.681 AC XY: 50463 AN XY: 74120

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.710

Alfa AF: 0.758 Hom.: 49387

Bravo AF: 0.670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	2.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs425667; hg19: -;