10-5525249-A-G

Variant names:

• chr10-5525249-A-G
• NM_005185.4:c.164A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005185.4(CALML3):​c.164A>G​(p.Glu55Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALML3 NM_005185.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.09
• Publications: 0 publications found

Genes affected

CALML3 (HGNC:1452): (calmodulin like 3) Predicted to enable calcium ion binding activity and enzyme regulator activity. Predicted to be involved in regulation of catalytic activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256462 (HGNC:):

CALML3-AS1 (HGNC:44682): (CALML3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005185.4. 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
	CALML3	NM_005185.4	MANE Select	c.164A>G	p.Glu55Gly	missense	Exon 1 of 1	NP_005176.1	P27482
	CALML3-AS1	NR_120496.1		n.115-829T>C		intron	N/A
	CALML3-AS1	NR_120497.1		n.114+884T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALML3	ENST00000315238.3	TSL:6 MANE Select	c.164A>G	p.Glu55Gly	missense	Exon 1 of 1	ENSP00000315299.1	P27482
	ENSG00000256462	ENST00000442008.2	TSL:4	n.322T>C		non_coding_transcript_exon	Exon 2 of 2
	CALML3-AS1	ENST00000542093.6	TSL:4	n.114+884T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.22
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.014
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		9.1
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.49
Sift4G	Uncertain	0.0020	D
Polyphen		0.15	B
Vest4		0.48
MutPred		0.69		Gain of glycosylation at S54 (P = 0.0507)
MVP		0.97
MPC		1.4
ClinPred		0.99	D
GERP RS		5.1
PromoterAI		-0.058	Neutral
Varity_R		0.63
gMVP		0.73
Mutation Taster		=28/72	disease causing

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

hg19: chr10-5567212;