Variant 19-14587676-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001204118.2(CLEC17A):c.184C>A(p.Leu62Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L62F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLEC17A
NM_001204118.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

CLEC17A (HGNC:34520): (C-type lectin domain containing 17A) Enables fucose binding activity; identical protein binding activity; and mannose binding activity. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

CLEC17A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22844273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC17A	NM_001204118.2 linkuse as main transcript	c.184C>A	p.Leu62Ile	missense_variant	3/14	ENST00000417570.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC17A	ENST00000417570.6 linkuse as main transcript	c.184C>A	p.Leu62Ile	missense_variant	3/14	1	NM_001204118.2	P1	Q6ZS10-1
CLEC17A	ENST00000339847.9 linkuse as main transcript	c.184C>A	p.Leu62Ile	missense_variant, NMD_transcript_variant	3/13	1			Q6ZS10-2
CLEC17A	ENST00000551730.1 linkuse as main transcript	c.184C>A	p.Leu62Ile	missense_variant, NMD_transcript_variant	3/14	1
CLEC17A	ENST00000547437.5 linkuse as main transcript	c.184C>A	p.Leu62Ile	missense_variant	3/13	2			Q6ZS10-3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

232924

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

126064

show subpopulations

Gnomad AFR exome

AF:

0.0000702

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000550

AC:

AN:

1453996

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722576

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.184C>A (p.L62I) alteration is located in exon 3 (coding exon 3) of the CLEC17A gene. This alteration results from a C to A substitution at nucleotide position 184, causing the leucine (L) at amino acid position 62 to be replaced by an isoleucine (I). 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

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.057

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.14

T;T

Polyphen

1.0

D;D

Vest4

0.31

MutPred

0.26

Loss of catalytic residue at L62 (P = 0.0137);Loss of catalytic residue at L62 (P = 0.0137);

MVP

0.70

MPC

3.0

ClinPred

0.51

GERP RS

2.3

Varity_R

0.14

gMVP

0.013

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over