Variant chr19-14597113-G-C 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.598G>C(p.Glu200Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CLEC17A
NM_001204118.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

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=0.12554312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC17A	NM_001204118.2 linkuse as main transcript	c.598G>C	p.Glu200Gln	missense_variant	10/14	ENST00000417570.6	NP_001191047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC17A	ENST00000417570.6 linkuse as main transcript	c.598G>C	p.Glu200Gln	missense_variant	10/14	1	NM_001204118.2	ENSP00000393719	P1	Q6ZS10-1
CLEC17A	ENST00000339847.9 linkuse as main transcript	c.598G>C	p.Glu200Gln	missense_variant, NMD_transcript_variant	10/13	1		ENSP00000341620		Q6ZS10-2
CLEC17A	ENST00000551730.1 linkuse as main transcript	c.598G>C	p.Glu200Gln	missense_variant, NMD_transcript_variant	10/14	1		ENSP00000447424
CLEC17A	ENST00000547437.5 linkuse as main transcript	c.598G>C	p.Glu200Gln	missense_variant	10/13	2		ENSP00000450065		Q6ZS10-3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

247638

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134354

show subpopulations

Gnomad AFR exome

AF:

0.000523

Gnomad AMR exome

AF:

0.0000292

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:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460938

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0000449

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:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000118

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000131

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

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000976

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 08, 2022

The c.598G>C (p.E200Q) alteration is located in exon 10 (coding exon 10) of the CLEC17A gene. This alteration results from a G to C substitution at nucleotide position 598, causing the glutamic acid (E) at amino acid position 200 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0048

.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.082

Sift

Benign

0.050

D;D

Sift4G

Uncertain

0.033

D;T

Polyphen

0.73

P;P

Vest4

0.26

MVP

0.66

MPC

0.19

ClinPred

0.057

GERP RS

2.3

Varity_R

0.096

gMVP

0.26

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