rs777356231

Variant names:

• chr5-134744021-C-T
• rs777356231
• NM_001745.4:c.668C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-134744021-C-T
• chr5-134744021-C-A
• chr5-134744021-C-G

Variant summary

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

The NM_001745.4(CAMLG):​c.668C>T​(p.Ala223Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000852 in 1,291,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: CAMLG NM_001745.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• Publications: 5 publications found

Genes affected

CAMLG (HGNC:1471): (calcium modulating ligand) The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin B, cyclosporin A binds and inactivates the key signaling intermediate calcineurin. The protein encoded by this gene functions similarly to cyclosporin A, binding to cyclophilin B and acting downstream of the TCR and upstream of calcineurin by causing an influx of calcium. This integral membrane protein appears to be a new participant in the calcium signal transduction pathway, implicating cyclophilin B in calcium signaling, even in the absence of cyclosporin. [provided by RefSeq, Jul 2008]

CAMLG Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type IIz

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001745.4. 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
	CAMLG	NM_001745.4	MANE Select	c.668C>T	p.Ala223Val	missense	Exon 3 of 4	NP_001736.1	P49069

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMLG	ENST00000297156.4	TSL:1 MANE Select	c.668C>T	p.Ala223Val	missense	Exon 3 of 4	ENSP00000297156.2	P49069
	CAMLG	ENST00000514518.1	TSL:1	c.207C>T	p.Cys69Cys	synonymous	Exon 2 of 3	ENSP00000427331.1	D6RIW3
	CAMLG	ENST00000918602.1		c.719C>T	p.Ala240Val	missense	Exon 4 of 5	ENSP00000588661.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000208 AC: 5 AN: 240056 AF XY: 0.0000231

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000852 AC: 11 AN: 1291006 Hom.: 0 Cov.: 20 AF XY: 0.00000922 AC XY: 6 AN XY: 650538

African (AFR) AF: 0.000100 AC: 3 AN: 30002

American (AMR) AF: 0.00 AC: 0 AN: 43780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24830

East Asian (EAS) AF: 0.00 AC: 0 AN: 38792

South Asian (SAS) AF: 0.0000368 AC: 3 AN: 81492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00000521 AC: 5 AN: 959638

Other (OTH) AF: 0.00 AC: 0 AN: 54518

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.13	T
Polyphen		0.97	D
Vest4		0.71
MutPred		0.50		Loss of helix (P = 0.079)
MVP		0.41
MPC		0.32
ClinPred		0.67	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.66
gMVP		0.79
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs777356231; hg19: chr5-134079711; COSMIC: COSV51804724;