NM_052964.4:c.1191T>C

Variant names:

• chr4-10490563-A-G
• rs189381725
• NM_052964.4:c.1191T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_052964.4(CLNK):​c.1191T>C​(p.Ile397Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,595,612 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (15 hom.)
• Consequence: CLNK NM_052964.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-10490563-A-G is Benign according to our data. Variant chr4-10490563-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2654671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.182 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

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.1191T>C	p.Ile397Ile	synonymous	Exon 19 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.1191T>C	p.Ile397Ile	synonymous	Exon 19 of 19	ENSP00000226951.6	Q7Z7G1-1
	CLNK	ENST00000515667.5	TSL:3	c.405T>C	p.Ile135Ile	synonymous	Exon 5 of 5	ENSP00000427256.1	D6RJB9
	ENSG00000287154	ENST00000663264.1		n.96+33723A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152172 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00655

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00445 AC: 971 AN: 218274 AF XY: 0.00440

Gnomad AFR exome AF: 0.000978

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.000741

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.00642

Gnomad OTH exome AF: 0.00253

GnomAD4 exome AF: 0.00543 AC: 7837 AN: 1443322 Hom.: 15 Cov.: 30 AF XY: 0.00522 AC XY: 3739 AN XY: 716234

African (AFR) AF: 0.000995 AC: 33 AN: 33158

American (AMR) AF: 0.00132 AC: 55 AN: 41820

Ashkenazi Jewish (ASJ) AF: 0.000970 AC: 25 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39278

South Asian (SAS) AF: 0.00207 AC: 172 AN: 83068

European-Finnish (FIN) AF: 0.0109 AC: 572 AN: 52632

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5750

European-Non Finnish (NFE) AF: 0.00609 AC: 6717 AN: 1102050

Other (OTH) AF: 0.00423 AC: 253 AN: 59792

GnomAD4 genome AF: 0.00436 AC: 664 AN: 152290 Hom.: 1 Cov.: 33 AF XY: 0.00406 AC XY: 302 AN XY: 74460

African (AFR) AF: 0.00116 AC: 48 AN: 41552

American (AMR) AF: 0.00294 AC: 45 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.00989 AC: 105 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00656 AC: 446 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00547 Hom.: 0

Bravo AF: 0.00354

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		-0.18
Mutation Taster		=98/2	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: rs189381725; hg19: chr4-10492187;