10-133326112-G-T

Variant names:

• chr10-133326112-G-T
• NM_015722.4:c.369C>A
• CALY p.Ile123Ile

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015722.4(CALY):​c.369C>A​(p.Ile123Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I123I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALY NM_015722.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 0 publications found

Genes affected

CALY (HGNC:17938): (calcyon neuron specific vesicular protein) The protein encoded by this gene is a type II single transmembrane protein. It is required for maximal stimulated calcium release after stimulation of purinergic or muscarinic but not beta-adrenergic receptors. The encoded protein interacts with D1 dopamine receptor and may interact with other DA receptor subtypes and/or GPCRs. [provided by RefSeq, Jul 2008]

ZNF511-PRAP1 (HGNC:38088): (ZNF511-PRAP1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ZNF511 (zinc finger protein 511) and PRAP1 (proline-rich acidic protein 1) genes on chromosome 10. The putative readthrough transcript may encode a fusion protein that shares sequence identity with each individual gene product and may be involved in the regulation of gene promoters, particularly those found on transfected plasmids. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-0.061 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015722.4. 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
	CALY	NM_015722.4	MANE Select	c.369C>A	p.Ile123Ile	synonymous	Exon 5 of 6	NP_056537.1	Q9NYX4-1
	CALY	NM_001321617.2		c.123C>A	p.Ile41Ile	synonymous	Exon 5 of 6	NP_001308546.1
	ZNF511-PRAP1	NM_001396060.1		c.680+14271G>T		intron	N/A	NP_001382989.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALY	ENST00000252939.9	TSL:1 MANE Select	c.369C>A	p.Ile123Ile	synonymous	Exon 5 of 6	ENSP00000252939.4	Q9NYX4-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+14271G>T		intron	N/A	ENSP00000357542.5	H7BY64
	CALY	ENST00000956089.1		c.489C>A	p.Ile163Ile	synonymous	Exon 5 of 6	ENSP00000626148.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.1
DANN	Benign	0.96
PhyloP100		-0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-135139616;