Variant chr10-133328970-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015722.4(CALY):c.20G>T(p.Ser7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,536 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: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CALY
NM_015722.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

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: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]

ZNF511-PRAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3469979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALY	NM_015722.4 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/6	ENST00000252939.9	NP_056537.1	Q9NYX4-1
CALY	NM_001321617.2 linkuse as main transcript	c.-387G>T		5_prime_UTR_variant	2/6		NP_001308546.1
ZNF511-PRAP1	NM_001396060.1 linkuse as main transcript	c.680+17129C>A		intron_variant			NP_001382989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CALY	ENST00000252939.9 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/6	1	NM_015722.4	ENSP00000252939.4	Q9NYX4-1
ZNF511-PRAP1	ENST00000368554.8 linkuse as main transcript	c.506+17129C>A		intron_variant		2		ENSP00000357542.5	H7BY64
CALY	ENST00000368555.3 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/3	2		ENSP00000357543.3	Q9NYX4-3
CALY	ENST00000368558.1 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/5	5		ENSP00000357546.1	Q9NYX4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412536

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000206

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 10, 2022

The c.20G>T (p.S7I) alteration is located in exon 2 (coding exon 1) of the CALY gene. This alteration results from a G to T substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by an isoleucine (I). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.83

T;T;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.29

MutPred

0.55

Loss of phosphorylation at S7 (P = 0.0437);Loss of phosphorylation at S7 (P = 0.0437);Loss of phosphorylation at S7 (P = 0.0437);

MVP

0.27

MPC

1.5

ClinPred

1.0

GERP RS

3.5

Varity_R

0.86

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

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

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