Variant 4-10501299-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052964.4(CLNK):c.1097G>A(p.Arg366Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

CLNK
NM_052964.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.169

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030635417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLNK	NM_052964.4 linkuse as main transcript	c.1097G>A	p.Arg366Lys	missense_variant	18/19	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3 linkuse as main transcript	c.1142G>A	p.Arg381Lys	missense_variant	18/19		XP_011512077.1
CLNK	XM_017007684.2 linkuse as main transcript	c.1142G>A	p.Arg381Lys	missense_variant	18/19		XP_016863173.1
LOC105374482	XR_925387.4 linkuse as main transcript	n.261+4744C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLNK	ENST00000226951.11 linkuse as main transcript	c.1097G>A	p.Arg366Lys	missense_variant	18/19	1	NM_052964.4	ENSP00000226951.6	Q7Z7G1-1
CLNK	ENST00000515667.5 linkuse as main transcript	c.311G>A	p.Arg104Lys	missense_variant	4/5	3		ENSP00000427256.1	D6RJB9
ENSG00000287154	ENST00000663264.1 linkuse as main transcript	n.97-28835C>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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 04, 2022

The c.1097G>A (p.R366K) alteration is located in exon 18 (coding exon 17) of the CLNK gene. This alteration results from a G to A substitution at nucleotide position 1097, causing the arginine (R) at amino acid position 366 to be replaced by a lysine (K). 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

0.070

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.4

DANN

Benign

0.95

DEOGEN2

Benign

0.17

T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.25

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.73

N;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.41

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.37

T;T;.

Sift4G

Benign

0.89

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.057

MutPred

0.33

Gain of ubiquitination at R366 (P = 0.0592);.;Gain of ubiquitination at R366 (P = 0.0592);

MVP

0.16

MPC

0.0066

ClinPred

0.88

GERP RS

1.6

Varity_R

0.068

gMVP

0.19

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over