chr7-128759009-A-G

Variant summary

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

The NM_001219.5(CALU):ā€‹c.554A>Gā€‹(p.Tyr185Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,461,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000031 ( 1 hom. )

Consequence

CALU
NM_001219.5 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44
Variant links:
Genes affected
CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

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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=0.38591826).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CALUNM_001219.5 linkuse as main transcriptc.554A>G p.Tyr185Cys missense_variant 4/7 ENST00000249364.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CALUENST00000249364.9 linkuse as main transcriptc.554A>G p.Tyr185Cys missense_variant 4/71 NM_001219.5 O43852-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000757
AC:
19
AN:
250944
Hom.:
1
AF XY:
0.000103
AC XY:
14
AN XY:
135596
show subpopulations
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 SAS exome
AF:
0.000556
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1461620
Hom.:
1
Cov.:
30
AF XY:
0.0000495
AC XY:
36
AN XY:
727118
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:
0.000499
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.000107
AC:
13
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsDec 08, 2023The c.578A>G (p.Y193C) alteration is located in exon 5 (coding exon 4) of the CALU gene. This alteration results from a A to G substitution at nucleotide position 578, causing the tyrosine (Y) at amino acid position 193 to be replaced by a cysteine (C). 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
0.45
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
.;.;D;.;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
D;D;D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.39
T;T;T;T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
1.6
L;.;L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.1
D;D;D;D;D
REVEL
Uncertain
0.43
Sift
Benign
0.044
D;T;T;T;T
Sift4G
Benign
0.16
T;T;T;T;T
Polyphen
0.91
.;.;P;.;.
Vest4
0.63
MutPred
0.38
Loss of phosphorylation at Y185 (P = 0.0171);.;Loss of phosphorylation at Y185 (P = 0.0171);Loss of phosphorylation at Y185 (P = 0.0171);.;
MVP
0.84
MPC
1.2
ClinPred
0.25
T
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.23
gMVP
0.71

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs777311637; hg19: chr7-128399063; API