7-128748762-C-G

Variant names:

• chr7-128748762-C-G
• rs1245347118
• NM_001219.5:c.179C>G

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.179C>G​(p.Thr60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. T60N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CALU NM_001219.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• 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=0.2062532).

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.179C>G	p.Thr60Ser	missense	Exon 2 of 7	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.203C>G	p.Thr68Ser	missense	Exon 3 of 8	NP_001186600.1	O43852-3
	CALU	NM_001199672.2		c.203C>G	p.Thr68Ser	missense	Exon 3 of 8	NP_001186601.1	O43852-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.179C>G	p.Thr60Ser	missense	Exon 2 of 7	ENSP00000249364.4	O43852-1
	CALU	ENST00000479257.5	TSL:1	c.203C>G	p.Thr68Ser	missense	Exon 3 of 8	ENSP00000420381.1	O43852-3
	CALU	ENST00000542996.7	TSL:1	c.203C>G	p.Thr68Ser	missense	Exon 3 of 8	ENSP00000438248.1	O43852-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.099
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.076
MutPred		0.33		Loss of phosphorylation at T60 (P = 0.0746)
MVP		0.39
MPC		0.30
ClinPred		0.68	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.26
gMVP		0.24
Mutation Taster		=70/30	polymorphism

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

dbSNP: rs1245347118; hg19: chr7-128388816;