Variant 4-10490534-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052964.4(CLNK):c.1220G>A(p.Gly407Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CLNK
NM_052964.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65

Variant links:

Genes affected

CLNK (HGNC:17438): (cytokine dependent hematopoietic cell linker) MIST is a member of the SLP76 family of adaptors (see LCP2, MIM 601603; BLNK, MIM 604515). MIST plays a role in the regulation of immunoreceptor signaling, including PLC-gamma (PLCG1; MIM 172420)-mediated B cell antigen receptor (BCR) signaling and FC-epsilon R1 (see FCER1A, MIM 147140)-mediated mast cell degranulation (Cao et al., 1999 [PubMed 10562326]; Goitsuka et al., 2000, 2001 [PubMed 10744659] [PubMed 11463797]).[supplied by OMIM, Mar 2008]

CLNK links:

ENSG00000287154 (HGNC:):

ENSG00000287154 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35366857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLNK	NM_052964.4 linkuse as main transcript	c.1220G>A	p.Gly407Glu	missense_variant	19/19	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3 linkuse as main transcript	c.1265G>A	p.Gly422Glu	missense_variant	19/19		XP_011512077.1
LOC105374482	XR_925387.4 linkuse as main transcript	n.83+1339C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLNK	ENST00000226951.11 linkuse as main transcript	c.1220G>A	p.Gly407Glu	missense_variant	19/19	1	NM_052964.4	ENSP00000226951.6	Q7Z7G1-1
CLNK	ENST00000515667.5 linkuse as main transcript	c.434G>A	p.Gly145Glu	missense_variant	5/5	3		ENSP00000427256.1	D6RJB9
ENSG00000287154	ENST00000663264.1 linkuse as main transcript	n.96+33694C>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241382

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130476

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000169

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457512

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724390

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

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 30, 2024

The c.1220G>A (p.G407E) alteration is located in exon 19 (coding exon 18) of the CLNK gene. This alteration results from a G to A substitution at nucleotide position 1220, causing the glycine (G) at amino acid position 407 to be replaced by a glutamic acid (E). 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

0.48

BayesDel_addAF

Benign

-0.0080

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;.;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D;.

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.40

MutPred

0.43

Gain of ubiquitination at K411 (P = 0.0315);.;Gain of ubiquitination at K411 (P = 0.0315);

MVP

0.45

MPC

0.031

ClinPred

0.95

GERP RS

4.1

Varity_R

0.21

gMVP

0.44

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