NM_001378452.1:c.57G>T

Variant names:

• chr3-4516548-G-T
• NM_001378452.1:c.57G>T

Variant summary

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

The NM_001378452.1(ITPR1):​c.57G>T​(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,084 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.484 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 62	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 61		NP_001161744.1
ITPR1	NM_001099952.4	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 59		NP_001093422.2
ITPR1	NM_002222.7	c.57G>T	p.Ala19Ala	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.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 62		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 62	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 62			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 61			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 61	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 1 of 59			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 59	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.57G>T	p.Ala19Ala	synonymous_variant	Exon 3 of 58	1		ENSP00000397885.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452084 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2 AN XY: 722182

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: 9.03e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr3-4558232;