rs202164310

Variant summary

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

The NM_006387.6(CHERP):​c.2378G>T​(p.Arg793Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R793H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHERP
NM_006387.6 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40
Variant links:
Genes affected
CHERP (HGNC:16930): (calcium homeostasis endoplasmic reticulum protein) Enables transmembrane transporter binding activity. Involved in positive regulation of calcineurin-NFAT signaling cascade and release of sequestered calcium ion into cytosol. Acts upstream of or within cellular calcium ion homeostasis and negative regulation of cell population proliferation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
C19orf44 (HGNC:26141): (chromosome 19 open reading frame 44)

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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=0.38436007).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHERPNM_006387.6 linkc.2378G>T p.Arg793Leu missense_variant Exon 15 of 17 ENST00000546361.7 NP_006378.3 Q8IWX8
C19orf44NM_032207.4 linkc.*180C>A 3_prime_UTR_variant Exon 9 of 9 ENST00000221671.8 NP_115583.1
C19orf44XM_006722920.5 linkc.*180C>A 3_prime_UTR_variant Exon 8 of 8 XP_006722983.1 M0R2B3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHERPENST00000546361.7 linkc.2378G>T p.Arg793Leu missense_variant Exon 15 of 17 1 NM_006387.6 ENSP00000439856.2 Q8IWX8
C19orf44ENST00000221671.8 linkc.*180C>A 3_prime_UTR_variant Exon 9 of 9 2 NM_032207.4 ENSP00000221671.2 Q9H6X5-1
ENSG00000141979ENST00000409035.1 linkn.*194-881G>T intron_variant Intron 6 of 11 2 ENSP00000386951.2 B8ZZF3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461162
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726908
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.25
T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.090
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Benign
0.070
Sift
Benign
0.21
T;T
Sift4G
Uncertain
0.058
T;T
Polyphen
0.50
P;.
Vest4
0.56
MutPred
0.29
Loss of methylation at R793 (P = 0.0295);.;
MVP
0.45
MPC
1.0
ClinPred
0.57
D
GERP RS
3.8
Varity_R
0.22
gMVP
0.55

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.

Other links and lift over

dbSNP: rs202164310; hg19: chr19-16631044; API