rs2838659

Variant names:

• chr21-44708323-G-A
• rs2838659
• NM_144991.3:c.82+3110C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 Gene-Disease associations (from GenCC):

• ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 98

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

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.82+3110C>T		intron	N/A	NP_659428.2
	TSPEAR	NM_001272037.2		c.-185+3110C>T		intron	N/A	NP_001258966.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.82+3110C>T		intron	N/A	ENSP00000321987.4	Q8WU66-1
	TSPEAR	ENST00000943283.1		c.82+3110C>T		intron	N/A	ENSP00000613342.1
	TSPEAR	ENST00000642437.1		n.82+3110C>T		intron	N/A	ENSP00000496535.1	A0A2R8YFK6

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

African (AFR) AF: 0.356 AC: 14721 AN: 41354

American (AMR) AF: 0.247 AC: 3767 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1410 AN: 5106

South Asian (SAS) AF: 0.420 AC: 2020 AN: 4812

European-Finnish (FIN) AF: 0.260 AC: 2753 AN: 10570

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15878 AN: 67936

Other (OTH) AF: 0.279 AC: 588 AN: 2110

Alfa AF: 0.247 Hom.: 18253

Bravo AF: 0.278

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs2838659; hg19: chr21-46128238;