rs12539499

Variant names:

• chr7-141930467-T-C
• rs12539499
• NM_013252.3:c.453-249A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-141930467-T-C
• chr7-141930467-T-G

Variant summary

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

The NM_013252.3(CLEC5A):​c.453-249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,150 control chromosomes in the GnomAD database, including 4,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4998 hom., cov: 32)
• Consequence: CLEC5A NM_013252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 7 publications found

Genes affected

CLEC5A (HGNC:2054): (C-type lectin domain containing 5A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined. [provided by RefSeq, Jul 2008]

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

MGAM Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LOC124901761 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013252.3. 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
	CLEC5A	NM_013252.3	MANE Select	c.453-249A>G		intron	N/A	NP_037384.1
	CLEC5A	NM_001301167.2		c.384-249A>G		intron	N/A	NP_001288096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC5A	ENST00000546910.6	TSL:1 MANE Select	c.453-249A>G		intron	N/A	ENSP00000449999.1
	CLEC5A	ENST00000551012.6	TSL:1	c.384-249A>G		intron	N/A	ENSP00000446890.2
	CLEC5A	ENST00000418498.5	TSL:1	n.*85-249A>G		intron	N/A	ENSP00000392561.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35703 AN: 152032 Hom.: 4999 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35702 AN: 152150 Hom.: 4998 Cov.: 32 AF XY: 0.237 AC XY: 17611 AN XY: 74354

African (AFR) AF: 0.0870 AC: 3614 AN: 41554

American (AMR) AF: 0.317 AC: 4841 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2334 AN: 5140

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4828

European-Finnish (FIN) AF: 0.274 AC: 2890 AN: 10560

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19229 AN: 67996

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.262 Hom.: 5732

Bravo AF: 0.235

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.30
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs12539499; hg19: chr7-141630267;