dbSNP rs749179971: CLNK:p.Glu380Gln (chr4-10501258-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052964.4(CLNK):c.1138G>C(p.Glu380Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CLNK
NM_052964.4 missense, splice_region

Scores

Splicing: ADA: 0.002198

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.641

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16378346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CLNK	NM_052964.4 link	c.1138G>C	p.Glu380Gln	missense_variant, splice_region_variant	Exon 18 of 19	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3 link	c.1183G>C	p.Glu395Gln	missense_variant, splice_region_variant	Exon 18 of 19		XP_011512077.1
CLNK	XM_017007684.2 link	c.1183G>C	p.Glu395Gln	missense_variant, splice_region_variant	Exon 18 of 19		XP_016863173.1
LOC105374482	XR_925387.4 link	n.261+4703C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLNK	ENST00000226951.11 link	c.1138G>C	p.Glu380Gln	missense_variant, splice_region_variant	Exon 18 of 19	1	NM_052964.4	ENSP00000226951.6	Q7Z7G1-1
CLNK	ENST00000515667.5 link	c.352G>C	p.Glu118Gln	missense_variant, splice_region_variant	Exon 4 of 5	3		ENSP00000427256.1	D6RJB9
ENSG00000287154	ENST00000663264.1 link	n.97-28876C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1417880

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704424

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:

9.11e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Uncertain

-0.033

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.3

N;D;.

REVEL

Benign

0.26

Sift

Benign

0.082

T;D;.

Sift4G

Uncertain

0.037

D;T;D

Polyphen

0.51

P;.;.

Vest4

0.14

MutPred

0.56

Loss of disorder (P = 0.1074);.;Loss of disorder (P = 0.1074);

MVP

0.27

MPC

0.012

ClinPred

0.80

GERP RS

3.6

Varity_R

0.089

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0022

dbscSNV1_RF

Benign

0.11

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

Computational scores

Splicing

Publications

Other links and lift over