Variant chr19-14592303-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001204118.2(CLEC17A):c.222G>T(p.Glu74Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,600,880 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CLEC17A
NM_001204118.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.72

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 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=0.045068562).

BP6

Variant 19-14592303-G-T is Benign according to our data. Variant chr19-14592303-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2383315.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC17A	NM_001204118.2 linkuse as main transcript	c.222G>T	p.Glu74Asp	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.222G>T	p.Glu74Asp	missense_variant	4/14	1	NM_001204118.2	ENSP00000393719	P1	Q6ZS10-1
CLEC17A	ENST00000339847.9 linkuse as main transcript	c.222G>T	p.Glu74Asp	missense_variant, NMD_transcript_variant	4/13	1		ENSP00000341620		Q6ZS10-2
CLEC17A	ENST00000551730.1 linkuse as main transcript	c.222G>T	p.Glu74Asp	missense_variant, NMD_transcript_variant	4/14	1		ENSP00000447424
CLEC17A	ENST00000547437.5 linkuse as main transcript	c.222G>T	p.Glu74Asp	missense_variant	4/13	2		ENSP00000450065		Q6ZS10-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000486

AC:

AN:

226402

Hom.:

AF XY:

0.0000489

AC XY:

AN XY:

122766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

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:

0.0000692

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000469

AC:

AN:

1448832

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

719786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000953

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:

0.0000561

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000828

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This 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

0.073

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.0050

DANN

Benign

0.71

DEOGEN2

Benign

0.0021

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.027

Sift

Benign

0.47

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0010

B;B

Vest4

0.12

MutPred

0.24

Loss of stability (P = 0.1508);Loss of stability (P = 0.1508);

MVP

0.19

MPC

1.6

ClinPred

0.059

GERP RS

-1.9

Varity_R

0.075

gMVP

0.0094

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