Variant 10-133326052-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015722.4(CALY):c.429C>A(p.Ser143Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 1,597,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CALY
NM_015722.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.703

Variant links:

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]

CALY links:

ZNF511-PRAP1 (HGNC:):

ZNF511-PRAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13952008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CALY	NM_015722.4 linkuse as main transcript	c.429C>A	p.Ser143Arg	missense_variant	5/6	ENST00000252939.9
ZNF511-PRAP1	NM_001396060.1 linkuse as main transcript	c.680+14211G>T		intron_variant
CALY	NM_001321617.2 linkuse as main transcript	c.183C>A	p.Ser61Arg	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALY	ENST00000252939.9 linkuse as main transcript	c.429C>A	p.Ser143Arg	missense_variant	5/6	1	NM_015722.4	P1	Q9NYX4-1
CALY	ENST00000368558.1 linkuse as main transcript	c.*214C>A		3_prime_UTR_variant	5/5	5			Q9NYX4-2
CALY	ENST00000467433.5 linkuse as main transcript	n.124C>A		non_coding_transcript_exon_variant	1/2	3
CALY	ENST00000467611.1 linkuse as main transcript	n.263C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000355

AC:

AN:

225102

Hom.:

AF XY:

0.0000162

AC XY:

AN XY:

123314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000692

AC:

AN:

1445176

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

717146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000231

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.429C>A (p.S143R) alteration is located in exon 5 (coding exon 4) of the CALY gene. This alteration results from a C to A substitution at nucleotide position 429, causing the serine (S) at amino acid position 143 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.096

Eigen

Benign

0.12

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.51

REVEL

Benign

0.23

Sift

Benign

0.99

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.37

MutPred

0.40

Gain of MoRF binding (P = 0.0357);

MVP

0.21

MPC

1.5

ClinPred

0.28

GERP RS

3.5

Varity_R

0.18

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over