Genetic Variant CHERP:p.Gly762Asp (chr19-16520424-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006387.6(CHERP):c.2285G>A(p.Gly762Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CHERP
NM_006387.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Publications

0 publications found

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]

CHERP links:

C19orf44 (HGNC:26141): (chromosome 19 open reading frame 44)

C19orf44 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

C19orf44 links:

ENSG00000141979 (HGNC:):

ENSG00000141979 links:

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ACMG classification

Classification was made for transcript

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=0.18861225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006387.6. 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
	CHERP	NM_006387.6	MANE Select	c.2285G>A	p.Gly762Asp	missense	Exon 14 of 17	NP_006378.3
	C19orf44	NM_032207.4	MANE Select	c.*371C>T		3_prime_UTR	Exon 9 of 9	NP_115583.1	Q9H6X5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHERP	ENST00000546361.7	TSL:1 MANE Select	c.2285G>A	p.Gly762Asp	missense	Exon 14 of 17	ENSP00000439856.2	Q8IWX8
C19orf44	ENST00000221671.8	TSL:2 MANE Select	c.*371C>T		3_prime_UTR	Exon 9 of 9	ENSP00000221671.2	Q9H6X5-1
C19orf44	ENST00000593380.1	TSL:1	n.*435C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000472255.1	Q9H6X5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249384

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

M_CAP

Benign

0.0099

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

3.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.70

REVEL

Benign

0.031

Sift

Benign

0.075

Sift4G

Benign

0.61

Polyphen

0.44

Vest4

0.41

MutPred

0.20

Gain of solvent accessibility (P = 0.0638)

MVP

0.41

MPC

1.0

ClinPred

0.29

GERP RS

4.7

Varity_R

0.15

gMVP

0.39

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over