LCK p.Val28Val

Variant names:

• chr1-32274410-A-A
• NM_005356.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-32274411--
• chr1-32274413-C-T
• chr1-32274413-C-A
• chr1-32274413-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005356.5(LCK):​c. variant causes a exon region 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: 32)
• Consequence: LCK NM_005356.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 0 publications found

Genes affected

LCK (HGNC:6524): (LCK proto-oncogene, Src family tyrosine kinase) This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. It contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to the plasma membrane and pericentrosomal vesicles, and binds to cell surface receptors, including CD4 and CD8, and other signaling molecules. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Aug 2016]

LCK Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to LCK deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005356.5. 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
	LCK	NM_005356.5	MANE Select	c.		exon_region	Exon 13 of 13	NP_005347.3
	LCK	NM_001439146.1		c.		exon_region	Exon 12 of 12	NP_001426075.1
	LCK	NM_001042771.3		c.		exon_region	Exon 13 of 13	NP_001036236.1	P06239-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCK	ENST00000336890.10	TSL:1 MANE Select	c.		exon_region	Exon 2 of 13	ENSP00000337825.5	P06239-1
	LCK	ENST00000333070.4	TSL:1	c.		exon_region	Exon 2 of 13	ENSP00000328213.4	P06239-3
	LCK	ENST00000469765.5	TSL:1	n.		exon_region	Exon 2 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-32740011;