chr19-16520400-C-A

Variant names:

• chr19-16520400-C-A
• rs373643502
• NM_006387.6:c.2309G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006387.6(CHERP):​c.2309G>T​(p.Arg770Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R770H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHERP NM_006387.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHERP	NM_006387.6	c.2309G>T	p.Arg770Leu	missense_variant	Exon 14 of 17	ENST00000546361.7	NP_006378.3
C19orf44	NM_032207.4	c.*347C>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000221671.8	NP_115583.1
C19orf44	XM_006722920.5	c.*347C>A		3_prime_UTR_variant	Exon 8 of 8		XP_006722983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHERP	ENST00000546361.7	c.2309G>T	p.Arg770Leu	missense_variant	Exon 14 of 17	1	NM_006387.6	ENSP00000439856.2
C19orf44	ENST00000221671.8	c.*347C>A		3_prime_UTR_variant	Exon 9 of 9	2	NM_032207.4	ENSP00000221671.2
ENSG00000141979	ENST00000409035.1	n.*194-1048G>T		intron_variant	Intron 6 of 11	2		ENSP00000386951.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.12
Sift	Benign	0.055	T;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.96	P;.
Vest4		0.53
MutPred		0.31		Loss of methylation at R770 (P = 0.038);.;
MVP		0.36
MPC		1.0
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.40
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs373643502; hg19: chr19-16631211;