NM_012198.5:c.238T>G

Variant names:

• chr2-162352383-T-G
• rs17783344
• NM_012198.5:c.238T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012198.5(GCA):​c.238T>G​(p.Ser80Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,582,658 control chromosomes in the GnomAD database, including 13,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.096 (922 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12415 hom.)
• Consequence: GCA NM_012198.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 37 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014909804).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012198.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCA	NM_012198.5	MANE Select	c.238T>G	p.Ser80Ala	missense	Exon 3 of 8	NP_036330.1
	GCA	NM_001330268.1		c.316T>G	p.Ser106Ala	missense	Exon 3 of 8	NP_001317197.1
	GCA	NM_001330265.1		c.283T>G	p.Ser95Ala	missense	Exon 4 of 9	NP_001317194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCA	ENST00000437150.7	TSL:1 MANE Select	c.238T>G	p.Ser80Ala	missense	Exon 3 of 8	ENSP00000394842.2
	GCA	ENST00000233612.8	TSL:2	c.181T>G	p.Ser61Ala	missense	Exon 3 of 8	ENSP00000233612.4
	GCA	ENST00000446271.5	TSL:5	c.316T>G	p.Ser106Ala	missense	Exon 3 of 5	ENSP00000393218.1

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14551 AN: 152098 Hom.: 922 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.106 AC: 26427 AN: 250464 AF XY: 0.109

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.0681

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.123 AC: 176333 AN: 1430442 Hom.: 12415 Cov.: 26 AF XY: 0.123 AC XY: 87544 AN XY: 713640

African (AFR) AF: 0.0248 AC: 819 AN: 33062

American (AMR) AF: 0.0718 AC: 3199 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5771 AN: 25882

East Asian (EAS) AF: 0.000355 AC: 14 AN: 39474

South Asian (SAS) AF: 0.0588 AC: 5031 AN: 85626

European-Finnish (FIN) AF: 0.110 AC: 5864 AN: 53362

Middle Eastern (MID) AF: 0.240 AC: 1361 AN: 5662

European-Non Finnish (NFE) AF: 0.136 AC: 146814 AN: 1083498

Other (OTH) AF: 0.126 AC: 7460 AN: 59306

GnomAD4 genome AF: 0.0956 AC: 14547 AN: 152216 Hom.: 922 Cov.: 32 AF XY: 0.0940 AC XY: 6994 AN XY: 74390

African (AFR) AF: 0.0261 AC: 1086 AN: 41570

American (AMR) AF: 0.103 AC: 1575 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.0579 AC: 279 AN: 4818

European-Finnish (FIN) AF: 0.0987 AC: 1046 AN: 10598

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9384 AN: 67966

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.129 Hom.: 5135

Bravo AF: 0.0947

TwinsUK AF: 0.142 AC: 525

ALSPAC AF: 0.145 AC: 559

ESP6500AA AF: 0.0318 AC: 140

ESP6500EA AF: 0.145 AC: 1247

ExAC AF: 0.107 AC: 12963

Asia WGS AF: 0.0320 AC: 113 AN: 3474

EpiCase AF: 0.155

EpiControl AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.082
MPC		0.094
ClinPred		0.010	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.44
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
SpliceAI score (max)		0.050		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: rs17783344; hg19: chr2-163208893; COSMIC: COSV107234515; COSMIC: COSV107234515;