rs146025689

Variant names:

• chr21-44529874-C-G
• NM_144991.3:c.714G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-44529874-C-G
• chr21-44529874-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144991.3(TSPEAR):​c.714G>C​(p.Ala238Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A238A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TSPEAR NM_144991.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.96

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]

LOC124905038 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-4.95 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPEAR	NM_144991.3	c.714G>C	p.Ala238Ala	synonymous_variant	Exon 5 of 12	ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.510G>C	p.Ala170Ala	synonymous_variant	Exon 6 of 13		NP_001258966.1
LOC124905038	XR_007067905.1	n.2366C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPEAR	ENST00000323084.9	c.714G>C	p.Ala238Ala	synonymous_variant	Exon 5 of 12	1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000397916.1	n.669G>C		non_coding_transcript_exon_variant	Exon 5 of 11	1
TSPEAR	ENST00000642437.1	n.*659G>C		non_coding_transcript_exon_variant	Exon 6 of 13			ENSP00000496535.1
TSPEAR	ENST00000642437.1	n.*659G>C		3_prime_UTR_variant	Exon 6 of 13			ENSP00000496535.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461308 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.066
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-45949757;