chr19-16519211-T-C

Position:

• chr19-16519211-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006387.6(CHERP):​c.2699A>G​(p.Asn900Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHERP NM_006387.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

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)

ENSG00000141979 (HGNC:):

ACMG classification

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=0.39674944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHERP	NM_006387.6	c.2699A>G	p.Asn900Ser	missense_variant	17/17	ENST00000546361.7	NP_006378.3
C19orf44	NM_032207.4	c.*41-883T>C		intron_variant		ENST00000221671.8	NP_115583.1
C19orf44	XM_006722920.5	c.*41-883T>C		intron_variant			XP_006722983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHERP	ENST00000546361.7	c.2699A>G	p.Asn900Ser	missense_variant	17/17	1	NM_006387.6	ENSP00000439856.2
C19orf44	ENST00000221671.8	c.*41-883T>C		intron_variant		2	NM_032207.4	ENSP00000221671.2
ENSG00000141979	ENST00000409035.1	n.*335A>G		non_coding_transcript_exon_variant	7/12	2		ENSP00000386951.2
ENSG00000141979	ENST00000409035.1	n.*335A>G		3_prime_UTR_variant	7/12	2		ENSP00000386951.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.2699A>G (p.N900S) alteration is located in exon 17 (coding exon 17) of the CHERP gene. This alteration results from a A to G substitution at nucleotide position 2699, causing the asparagine (N) at amino acid position 900 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.070
Sift	Benign	0.34	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.77	P;.
Vest4		0.62
MutPred		0.27		Gain of phosphorylation at N900 (P = 0.017);.;
MVP		0.49
MPC		0.64
ClinPred		0.44	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-16630022;