12-10071484-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016511.4(CLEC1A):​c.692C>T​(p.Pro231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.527
Variant links:
Genes affected
CLEC1A (HGNC:24355): (C-type lectin domain family 1 member A) 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 signaling, glycoprotein turnover, and roles in inflammation and immune response. The encoded protein may play a role in regulating dendritic cell function. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04025477).
BP6
Variant 12-10071484-G-A is Benign according to our data. Variant chr12-10071484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2542412.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLEC1ANM_016511.4 linkuse as main transcriptc.692C>T p.Pro231Leu missense_variant 6/6 ENST00000315330.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLEC1AENST00000315330.8 linkuse as main transcriptc.692C>T p.Pro231Leu missense_variant 6/61 NM_016511.4 P1
CLEC1AENST00000457018.6 linkuse as main transcriptc.593C>T p.Pro198Leu missense_variant 5/52
CLEC1AENST00000420265.2 linkuse as main transcriptc.416C>T p.Pro139Leu missense_variant 4/42

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459080
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725656
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 03, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
8.3
DANN
Benign
0.72
DEOGEN2
Benign
0.0072
T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0012
N
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.040
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.025
N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.76
N;N;N
REVEL
Benign
0.026
Sift
Benign
0.30
T;T;T
Sift4G
Benign
0.23
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.029
MutPred
0.39
Gain of catalytic residue at P231 (P = 0.1128);.;.;
MVP
0.42
MPC
0.037
ClinPred
0.14
T
GERP RS
0.44
Varity_R
0.036
gMVP
0.29

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: chr12-10224083; API