rs183771991

Variant names:

• chr4-10525844-C-A
• rs183771991
• NM_052964.4:c.728G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-10525844-C-A
• chr4-10525844-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052964.4(CLNK):​c.728G>T​(p.Ser243Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000603 in 1,574,478 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (1 hom.)
• Consequence: CLNK NM_052964.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 4 publications found

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:58732):

LOC105374482 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006952852).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052964.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLNK	NM_052964.4	MANE Select	c.728G>T	p.Ser243Ile	missense	Exon 14 of 19	NP_443196.2	Q7Z7G1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLNK	ENST00000226951.11	TSL:1 MANE Select	c.728G>T	p.Ser243Ile	missense	Exon 14 of 19	ENSP00000226951.6	Q7Z7G1-1
	ENSG00000287154	ENST00000663264.1		n.97-4290C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000375 AC: 76 AN: 202836 AF XY: 0.000351

Gnomad AFR exome AF: 0.000245

Gnomad AMR exome AF: 0.000960

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000457

Gnomad OTH exome AF: 0.000963

GnomAD4 exome AF: 0.000643 AC: 914 AN: 1422204 Hom.: 1 Cov.: 28 AF XY: 0.000612 AC XY: 431 AN XY: 704706

African (AFR) AF: 0.0000914 AC: 3 AN: 32818

American (AMR) AF: 0.000930 AC: 37 AN: 39798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 38798

South Asian (SAS) AF: 0.00 AC: 0 AN: 81180

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.000790 AC: 859 AN: 1087930

Other (OTH) AF: 0.000237 AC: 14 AN: 59010

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74454

African (AFR) AF: 0.000192 AC: 8 AN: 41566

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000474 Hom.: 0

Bravo AF: 0.000400

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000541 AC: 2

ESP6500EA AF: 0.000489 AC: 4

ExAC AF: 0.000291 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.084
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.87	P
Vest4		0.17
MVP		0.048
MPC		0.0074
ClinPred		0.025	T
GERP RS		3.0
Varity_R		0.12
gMVP		0.36
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs183771991; hg19: chr4-10527468;