19-16525274-C-T

Variant names:

• chr19-16525274-C-T
• rs780148993
• NM_006387.6:c.1709G>A

Variant summary

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

The NM_006387.6(CHERP):​c.1709G>A​(p.Arg570His) variant causes a missense change. The variant allele was found at a frequency of 0.00000156 in 1,282,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CHERP NM_006387.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38
• Publications: 0 publications found

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]

ENSG00000141979 (HGNC:):

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=0.21401224).

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.1709G>A	p.Arg570His	missense	Exon 10 of 17	NP_006378.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHERP	ENST00000546361.7	TSL:1 MANE Select	c.1709G>A	p.Arg570His	missense	Exon 10 of 17	ENSP00000439856.2	Q8IWX8
	ENSG00000141979	ENST00000409035.1	TSL:2	n.*194-5922G>A		intron	N/A	ENSP00000386951.2	B8ZZF3
	CHERP	ENST00000862402.1		c.1709G>A	p.Arg570His	missense	Exon 10 of 17	ENSP00000532461.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1282034 Hom.: 0 Cov.: 32 AF XY: 0.00000323 AC XY: 2 AN XY: 620104

African (AFR) AF: 0.00 AC: 0 AN: 25964

American (AMR) AF: 0.00 AC: 0 AN: 18308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18156

East Asian (EAS) AF: 0.00 AC: 0 AN: 32340

South Asian (SAS) AF: 0.0000165 AC: 1 AN: 60476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4790

European-Non Finnish (NFE) AF: 9.77e-7 AC: 1 AN: 1023962

Other (OTH) AF: 0.00 AC: 0 AN: 52876

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000201 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.23
Sift	Benign	0.11	T
Sift4G	Benign	0.37	T
Polyphen		0.069	B
Vest4		0.27
MutPred		0.18		Gain of relative solvent accessibility (P = 0.1571)
MVP		0.58
MPC		2.1
ClinPred		0.67	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.29
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs780148993; hg19: chr19-16636085;