NM_015722.4:c.142A>G

Variant names:

• chr10-133328009-T-C
• rs11550437
• NM_015722.4:c.142A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015722.4(CALY):​c.142A>G​(p.Ile48Val) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I48F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALY NM_015722.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14034268).

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.142A>G	p.Ile48Val	missense	Exon 3 of 6	NP_056537.1	Q9NYX4-1
	CALY	NM_001321617.2		c.-265A>G		5_prime_UTR	Exon 3 of 6	NP_001308546.1
	ZNF511-PRAP1	NM_001396060.1		c.680+16168T>C		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.142A>G	p.Ile48Val	missense	Exon 3 of 6	ENSP00000252939.4	Q9NYX4-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+16168T>C		intron	N/A	ENSP00000357542.5	H7BY64
	CALY	ENST00000956089.1		c.142A>G	p.Ile48Val	missense	Exon 3 of 6	ENSP00000626148.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.88	L
PhyloP100		1.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	0.34	T
Polyphen		0.98	D
Vest4		0.28
MutPred		0.53		Gain of phosphorylation at T50 (P = 0.2368)
MVP		0.12
MPC		1.0
ClinPred		0.44	T
GERP RS		3.2
Varity_R		0.041
gMVP		0.34
Mutation Taster		=87/13	polymorphism

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: rs11550437; hg19: chr10-135141513;