Variant chr19-14592314-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001204118.2(CLEC17A):c.233A>G(p.Tyr78Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CLEC17A
NM_001204118.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC17A	NM_001204118.2 linkuse as main transcript	c.233A>G	p.Tyr78Cys	missense_variant	4/14	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.233A>G	p.Tyr78Cys	missense_variant	4/14	1	NM_001204118.2	ENSP00000393719	P1	Q6ZS10-1
CLEC17A	ENST00000339847.9 linkuse as main transcript	c.233A>G	p.Tyr78Cys	missense_variant, NMD_transcript_variant	4/13	1		ENSP00000341620		Q6ZS10-2
CLEC17A	ENST00000551730.1 linkuse as main transcript	c.233A>G	p.Tyr78Cys	missense_variant, NMD_transcript_variant	4/14	1		ENSP00000447424
CLEC17A	ENST00000547437.5 linkuse as main transcript	c.233A>G	p.Tyr78Cys	missense_variant	4/13	2		ENSP00000450065		Q6ZS10-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000433

AC:

AN:

231098

Hom.:

AF XY:

0.00000798

AC XY:

AN XY:

125306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000312

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:

0.00000276

AC:

AN:

1451748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721396

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

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:

0.00000181

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

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

Jan 25, 2023

The c.233A>G (p.Y78C) alteration is located in exon 4 (coding exon 4) of the CLEC17A gene. This alteration results from a A to G substitution at nucleotide position 233, causing the tyrosine (Y) at amino acid position 78 to be replaced by a cysteine (C). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0062

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.8

D;N

REVEL

Benign

0.18

Sift

Benign

0.073

T;T

Sift4G

Benign

0.087

T;T

Polyphen

1.0

D;D

Vest4

0.54

MutPred

0.24

Loss of phosphorylation at Y78 (P = 0);Loss of phosphorylation at Y78 (P = 0);

MVP

0.72

MPC

3.7

ClinPred

0.50

GERP RS

1.2

Varity_R

0.21

gMVP

0.048

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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