rs2275723

Variant names:

• chr10-133326131-G-A
• rs2275723
• NM_015722.4:c.361-11C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321617.2(CALY):​c.104C>T​(p.Pro35Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,591,104 control chromosomes in the GnomAD database, including 9,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.091 (794 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8732 hom.)
• Consequence: CALY NM_001321617.2 missense
• Scores: Splicing: ADA: 0.00005574
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321617.2. 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.361-11C>T		intron	N/A	NP_056537.1	Q9NYX4-1
	CALY	NM_001321617.2		c.104C>T	p.Pro35Leu	missense	Exon 5 of 6	NP_001308546.1
	ZNF511-PRAP1	NM_001396060.1		c.680+14290G>A		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.361-11C>T		intron	N/A	ENSP00000252939.4	Q9NYX4-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+14290G>A		intron	N/A	ENSP00000357542.5	H7BY64
	CALY	ENST00000956089.1		c.470C>T	p.Pro157Leu	missense	Exon 5 of 6	ENSP00000626148.1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13866 AN: 152122 Hom.: 790 Cov.: 33

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.106 AC: 24005 AN: 226346 AF XY: 0.104

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.0772

Gnomad EAS exome AF: 0.0347

Gnomad FIN exome AF: 0.0748

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.106 AC: 153088 AN: 1438864 Hom.: 8732 Cov.: 32 AF XY: 0.106 AC XY: 75403 AN XY: 712566

African (AFR) AF: 0.0421 AC: 1392 AN: 33052

American (AMR) AF: 0.187 AC: 8104 AN: 43326

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 1934 AN: 25518

East Asian (EAS) AF: 0.0563 AC: 2195 AN: 38960

South Asian (SAS) AF: 0.0958 AC: 8068 AN: 84254

European-Finnish (FIN) AF: 0.0774 AC: 3971 AN: 51336

Middle Eastern (MID) AF: 0.105 AC: 598 AN: 5686

European-Non Finnish (NFE) AF: 0.110 AC: 120672 AN: 1097516

Other (OTH) AF: 0.104 AC: 6154 AN: 59216

GnomAD4 genome AF: 0.0912 AC: 13883 AN: 152240 Hom.: 794 Cov.: 33 AF XY: 0.0900 AC XY: 6697 AN XY: 74434

African (AFR) AF: 0.0440 AC: 1827 AN: 41568

American (AMR) AF: 0.155 AC: 2372 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.0484 AC: 250 AN: 5166

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4824

European-Finnish (FIN) AF: 0.0714 AC: 757 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7469 AN: 67992

Other (OTH) AF: 0.101 AC: 214 AN: 2116

Alfa AF: 0.101 Hom.: 1401

Bravo AF: 0.0953

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs2275723; hg19: chr10-135139635; COSMIC: COSV53310633; COSMIC: COSV53310633;