NM_031468.4:c.149C>T

Variant names:

• chr7-72278781-G-A
• rs764214080
• NM_031468.4:c.149C>T

Variant summary

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

The NM_031468.4(CALN1):​c.149C>T​(p.Ala50Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,456 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: 6.8e-7 (0 hom.)
• Consequence: CALN1 NM_031468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.23
• Publications: 0 publications found

Genes affected

CALN1 (HGNC:13248): (calneuron 1) This gene encodes a protein with high similarity to the calcium-binding proteins of the calmodulin family. The encoded protein contains two EF-hand domains and potential calcium-binding sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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_031468.4. 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
	CALN1	NM_031468.4	MANE Select	c.149C>T	p.Ala50Val	missense	Exon 3 of 7	NP_113656.2	Q9BXU9-2
	CALN1	NM_001017440.3		c.23C>T	p.Ala8Val	missense	Exon 2 of 6	NP_001017440.1	Q9BXU9-1
	CALN1	NM_001363460.1		c.23C>T	p.Ala8Val	missense	Exon 2 of 6	NP_001350389.1	A4D1Z1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALN1	ENST00000395275.7	TSL:5 MANE Select	c.149C>T	p.Ala50Val	missense	Exon 3 of 7	ENSP00000378690.2	Q9BXU9-2
	CALN1	ENST00000329008.9	TSL:1	c.23C>T	p.Ala8Val	missense	Exon 2 of 6	ENSP00000332498.5	Q9BXU9-1
	CALN1	ENST00000395276.6	TSL:1	c.23C>T	p.Ala8Val	missense	Exon 3 of 7	ENSP00000378691.2	Q9BXU9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461456 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726952

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111710

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

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	0.64
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.55	N
PhyloP100		9.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Benign	0.047	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.95	P
Vest4		0.81
MutPred		0.34		Gain of helix (P = 0.0117)
MVP		0.69
MPC		1.8
ClinPred		0.92	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.85
Mutation Taster		=61/39	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: rs764214080; hg19: chr7-71743766;