3-4516509-T-A

Variant names:

• chr3-4516509-T-A
• NM_001378452.1:c.18T>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001378452.1(ITPR1):​c.18T>A​(p.Ser6Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,436,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0450

Genes affected

ITPR1 (HGNC:6180): (inositol 1,4,5-trisphosphate receptor type 1) This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

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=-0.39).
• BP6: Variant 3-4516509-T-A is Benign according to our data. Variant chr3-4516509-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3606980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.045 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 61		NP_001161744.1
ITPR1	NM_001099952.4	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 59		NP_001093422.2
ITPR1	NM_002222.7	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 58		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 1 of 59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.18T>A	p.Ser6Ser	synonymous_variant	Exon 3 of 58	1		ENSP00000397885.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1436218 Hom.: 0 Cov.: 28 AF XY: 0.00000420 AC XY: 3 AN XY: 714154

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: 0.00000182

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.7
DANN	Benign	0.77

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: chr3-4558193;