10-133325906-G-C

Variant names:

• chr10-133325906-G-C
• rs987402732
• NM_015722.4:c.575C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015722.4(CALY):​c.575C>G​(p.Pro192Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,293,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (1 hom.)
• Consequence: CALY NM_015722.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09421486).

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.575C>G	p.Pro192Arg	missense	Exon 5 of 6	NP_056537.1	Q9NYX4-1
	CALY	NM_001321617.2		c.329C>G	p.Pro110Arg	missense	Exon 5 of 6	NP_001308546.1
	ZNF511-PRAP1	NM_001396060.1		c.680+14065G>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.575C>G	p.Pro192Arg	missense	Exon 5 of 6	ENSP00000252939.4	Q9NYX4-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+14065G>C		intron	N/A	ENSP00000357542.5	H7BY64
	CALY	ENST00000956089.1		c.695C>G	p.Pro232Arg	missense	Exon 5 of 6	ENSP00000626148.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152002 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000210 AC: 3 AN: 14256 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000359 AC: 41 AN: 1141990 Hom.: 1 Cov.: 30 AF XY: 0.0000402 AC XY: 22 AN XY: 547484

African (AFR) AF: 0.00 AC: 0 AN: 23500

American (AMR) AF: 0.00 AC: 0 AN: 9790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15624

East Asian (EAS) AF: 0.00 AC: 0 AN: 26750

South Asian (SAS) AF: 0.00115 AC: 40 AN: 34732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3166

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 951646

Other (OTH) AF: 0.0000216 AC: 1 AN: 46198

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152002 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74246

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.093
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.014	D
Polyphen		0.92	P
Vest4		0.13
MutPred		0.35		Gain of MoRF binding (P = 0.012)
MVP		0.082
MPC		0.58
ClinPred		0.12	T
GERP RS		3.5
Varity_R		0.087
gMVP		0.23
Mutation Taster		=95/5	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: rs987402732; hg19: chr10-135139410;