7-71810446-T-G

Variant names:

• chr7-71810446-T-G
• NM_031468.4:c.548A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031468.4(CALN1):​c.548A>C​(p.Tyr183Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALN1 NM_031468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.01

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALN1	NM_031468.4	c.548A>C	p.Tyr183Ser	missense_variant	Exon 6 of 7	ENST00000395275.7	NP_113656.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALN1	ENST00000395275.7	c.548A>C	p.Tyr183Ser	missense_variant	Exon 6 of 7	5	NM_031468.4	ENSP00000378690.2
CALN1	ENST00000329008.9	c.422A>C	p.Tyr141Ser	missense_variant	Exon 5 of 6	1		ENSP00000332498.5
CALN1	ENST00000395276.6	c.422A>C	p.Tyr141Ser	missense_variant	Exon 6 of 7	1		ENSP00000378691.2
CALN1	ENST00000431984.5	c.422A>C	p.Tyr141Ser	missense_variant	Exon 5 of 6	1		ENSP00000410704.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.548A>C (p.Y183S) alteration is located in exon 6 (coding exon 5) of the CALN1 gene. This alteration results from a A to C substitution at nucleotide position 548, causing the tyrosine (Y) at amino acid position 183 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.055	T;.;T;.;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	.;D;.;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.97	L;.;L;.;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.5	D;D;D;.;D
REVEL	Benign	0.27
Sift	Benign	0.26	T;T;T;.;T
Sift4G	Benign	0.35	T;T;T;D;T
Polyphen		0.82	P;.;P;.;P
Vest4		0.62
MutPred		0.65		Loss of stability (P = 0.1253);.;Loss of stability (P = 0.1253);.;Loss of stability (P = 0.1253);
MVP		0.76
MPC		1.5
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.50
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-71275431;