NM_001219.5:c.268G>A

Variant names:

• chr7-128754308-G-A
• NM_001219.5:c.268G>A

Variant summary

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

The NM_001219.5(CALU):​c.268G>A​(p.Val90Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALU NM_001219.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

Genes affected

CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

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=0.24065429).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001219.5. 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
	CALU	NM_001219.5	MANE Select	c.268G>A	p.Val90Met	missense	Exon 3 of 7	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.292G>A	p.Val98Met	missense	Exon 4 of 8	NP_001186600.1	O43852-3
	CALU	NM_001199673.2		c.268G>A	p.Val90Met	missense	Exon 3 of 6	NP_001186602.1	O43852-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.268G>A	p.Val90Met	missense	Exon 3 of 7	ENSP00000249364.4	O43852-1
	CALU	ENST00000479257.5	TSL:1	c.292G>A	p.Val98Met	missense	Exon 4 of 8	ENSP00000420381.1	O43852-3
	CALU	ENST00000535011.6	TSL:1	c.268G>A	p.Val90Met	missense	Exon 3 of 6	ENSP00000442110.1	O43852-10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.037
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.76	N
PhyloP100		2.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.19
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.40
MutPred		0.22		Gain of loop (P = 0.1069)
MVP		0.67
ClinPred		0.43	T
GERP RS		6.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.10
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-128394362;