rs183434214

Variant names:

• chr21-44509141-G-A
• rs183434214
• NM_144991.3:c.1754+58C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44509141-G-A
• chr21-44509141-G-C
• chr21-44509141-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_144991.3(TSPEAR):​c.1754+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000848 in 1,560,958 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (6 hom.)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-44509141-G-A is Benign according to our data. Variant chr21-44509141-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1195719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00461 (702/152258) while in subpopulation AFR AF = 0.0161 (670/41538). AF 95% confidence interval is 0.0151. There are 7 homozygotes in GnomAd4. There are 314 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144991.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPEAR	NM_144991.3	MANE Select	c.1754+58C>T		intron	N/A	NP_659428.2
	TSPEAR	NM_001272037.2		c.1550+58C>T		intron	N/A	NP_001258966.1
	TSPEAR-AS1	NR_103707.1		n.1215-111G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.1754+58C>T		intron	N/A	ENSP00000321987.4	Q8WU66-1
	TSPEAR	ENST00000397916.1	TSL:1	n.1709+58C>T		intron	N/A
	TSPEAR	ENST00000943283.1		c.1754+58C>T		intron	N/A	ENSP00000613342.1

Frequencies

GnomAD3 genomes AF: 0.00463 AC: 705 AN: 152140 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.000441 AC: 621 AN: 1408700 Hom.: 6 Cov.: 27 AF XY: 0.000374 AC XY: 261 AN XY: 697284

African (AFR) AF: 0.0147 AC: 478 AN: 32586

American (AMR) AF: 0.000914 AC: 39 AN: 42680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24350

East Asian (EAS) AF: 0.00 AC: 0 AN: 39036

South Asian (SAS) AF: 0.0000370 AC: 3 AN: 81108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51102

Middle Eastern (MID) AF: 0.000737 AC: 4 AN: 5424

European-Non Finnish (NFE) AF: 0.0000344 AC: 37 AN: 1074082

Other (OTH) AF: 0.00103 AC: 60 AN: 58332

GnomAD4 genome AF: 0.00461 AC: 702 AN: 152258 Hom.: 7 Cov.: 32 AF XY: 0.00422 AC XY: 314 AN XY: 74446

African (AFR) AF: 0.0161 AC: 670 AN: 41538

American (AMR) AF: 0.00124 AC: 19 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.0000695 Hom.: 0

Bravo AF: 0.00532

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.38
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs183434214; hg19: chr21-45929024;