chr4-10501313-T-C

Variant names:

• chr4-10501313-T-C
• rs2903960
• NM_052964.4:c.1083A>G

Variant summary

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

The NM_052964.4(CLNK):​c.1083A>G​(p.Ile361Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLNK NM_052964.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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]

ENSG00000287154 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
CLNK	NM_052964.4	c.1083A>G	p.Ile361Met	missense_variant	Exon 18 of 19	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3	c.1128A>G	p.Ile376Met	missense_variant	Exon 18 of 19		XP_011512077.1
CLNK	XM_017007684.2	c.1128A>G	p.Ile376Met	missense_variant	Exon 18 of 19		XP_016863173.1
LOC105374482	XR_925387.4	n.261+4758T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLNK	ENST00000226951.11	c.1083A>G	p.Ile361Met	missense_variant	Exon 18 of 19	1	NM_052964.4	ENSP00000226951.6
CLNK	ENST00000515667.5	c.297A>G	p.Ile99Met	missense_variant	Exon 4 of 5	3		ENSP00000427256.1
ENSG00000287154	ENST00000663264.1	n.97-28821T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.87e-7 AC: 1 AN: 1455132 Hom.: 0 Cov.: 45 AF XY: 0.00000138 AC XY: 1 AN XY: 723818

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: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	4.3	H;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D;D;.
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.69
MutPred		0.65		Gain of MoRF binding (P = 0.0957);.;Gain of MoRF binding (P = 0.0957);
MVP		0.33
MPC		0.035
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.51
gMVP		0.50

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

Other links and lift over

dbSNP: rs2903960; hg19: chr4-10502937;