chr2-162347693-C-G

Variant names:

• chr2-162347693-C-G
• NM_012198.5:c.143C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012198.5(GCA):​c.143C>G​(p.Ser48Cys) 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. 14/22 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: GCA NM_012198.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

GCA (HGNC:15990): (grancalcin) This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.276433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCA	NM_012198.5	c.143C>G	p.Ser48Cys	missense_variant	Exon 2 of 8	ENST00000437150.7	NP_036330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCA	ENST00000437150.7	c.143C>G	p.Ser48Cys	missense_variant	Exon 2 of 8	1	NM_012198.5	ENSP00000394842.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143C>G (p.S48C) alteration is located in exon 2 (coding exon 2) of the GCA gene. This alteration results from a C to G substitution at nucleotide position 143, causing the serine (S) at amino acid position 48 to be replaced by a cysteine (C). 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	Benign	0.085
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T;.;.
Eigen	Benign	0.027
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Uncertain	0.086	D
MutationAssessor	Benign	1.8	.;.;L;.;.
PhyloP100		2.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D;D;D;T;T
Sift4G	Uncertain	0.052	T;T;T;T;T
Polyphen		1.0	.;.;D;.;.
Vest4		0.43, 0.34, 0.38
MutPred		0.28		.;.;Loss of disorder (P = 0.0081);.;.;
MVP		0.97
MPC		0.39
ClinPred		0.73	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.51
Mutation Taster		=72/28	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

hg19: chr2-163204203;