Variant 19-16525376-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006387.6(CHERP):c.1607A>G(p.Asn536Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,495,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CHERP
NM_006387.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

CHERP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05160612).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHERP	NM_006387.6 linkuse as main transcript	c.1607A>G	p.Asn536Ser	missense_variant	10/17	ENST00000546361.7	NP_006378.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CHERP	ENST00000546361.7 linkuse as main transcript	c.1607A>G	p.Asn536Ser	missense_variant	10/17	1	NM_006387.6	ENSP00000439856	P3
CHERP	ENST00000198939.6 linkuse as main transcript	c.1640A>G	p.Asn547Ser	missense_variant	10/17	5		ENSP00000198939	A1
CHERP	ENST00000544299.5 linkuse as main transcript	n.409A>G		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000473

AC:

AN:

126776

Hom.:

AF XY:

0.0000745

AC XY:

AN XY:

67098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000522

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1343650

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

656762

show subpopulations

Gnomad4 AFR exome

AF:

0.0000688

Gnomad4 AMR exome

AF:

0.0000363

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000139

Gnomad4 SAS exome

AF:

0.0000442

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000758

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000255

AC:

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

Nov 21, 2023

The c.1607A>G (p.N536S) alteration is located in exon 10 (coding exon 10) of the CHERP gene. This alteration results from a A to G substitution at nucleotide position 1607, causing the asparagine (N) at amino acid position 536 to be replaced by a serine (S). 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

Benign

0.069

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;.

Eigen

Benign

0.075

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.052

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.26

Sift

Benign

0.084

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.99

D;.

Vest4

0.22

MutPred

0.11

Gain of glycosylation at N536 (P = 0.0394);.;

MVP

0.62

MPC

1.7

ClinPred

0.17

GERP RS

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.54

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.

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