rs376761519

Variant names:

• chr10-133326943-C-A
• rs376761519
• NM_015722.4:c.295G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133326943-C-A
• chr10-133326943-C-T

Variant summary

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

The NM_001321617.2(CALY):​c.-112G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CALY NM_001321617.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• 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=0.19368535).

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.295G>T	p.Val99Leu	missense	Exon 4 of 6	NP_056537.1	Q9NYX4-1
	CALY	NM_001321617.2		c.-112G>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 6	NP_001308546.1
	CALY	NM_001321617.2		c.-112G>T		5_prime_UTR	Exon 4 of 6	NP_001308546.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALY	ENST00000252939.9	TSL:1 MANE Select	c.295G>T	p.Val99Leu	missense	Exon 4 of 6	ENSP00000252939.4	Q9NYX4-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+15102C>A		intron	N/A	ENSP00000357542.5	H7BY64
	CALY	ENST00000956089.1		c.295G>T	p.Val99Leu	missense	Exon 4 of 6	ENSP00000626148.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458984 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725480

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111470

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.5
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.096
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.050
Sift	Benign	0.23	T
Sift4G	Benign	0.18	T
Polyphen		0.020	B
Vest4		0.19
MutPred		0.74		Gain of helix (P = 0.0696)
MVP		0.093
MPC		0.60
ClinPred		0.15	T
GERP RS		2.4
Varity_R		0.15
gMVP		0.29
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs376761519; hg19: chr10-135140447;