rs766580359

Variant names:

• chr1-32276337-A-G
• NM_005356.5:c.632A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-32276337-A-G
• chr1-32276337-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005356.5(LCK):​c.632A>G​(p.Asn211Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,423,532 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N211I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LCK NM_005356.5 missense, splice_region
• Scores: Splicing: ADA: 0.0007359
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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]

ACMG classification

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=0.1624147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCK	NM_005356.5	c.632A>G	p.Asn211Ser	missense_variant, splice_region_variant	Exon 8 of 13	ENST00000336890.10	NP_005347.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCK	ENST00000336890.10	c.632A>G	p.Asn211Ser	missense_variant, splice_region_variant	Exon 8 of 13	1	NM_005356.5	ENSP00000337825.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1423532 Hom.: 0 Cov.: 32 AF XY: 0.00000283 AC XY: 2 AN XY: 705666

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: 0.00000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.21	T;T;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.58	N;N;.;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.76	N;.;N;N
REVEL	Benign	0.064
Sift	Benign	0.055	T;.;T;T
Sift4G	Benign	0.52	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.14
MutPred		0.33		Gain of catalytic residue at N211 (P = 0.0067);Gain of catalytic residue at N211 (P = 0.0067);.;Gain of catalytic residue at N211 (P = 0.0067);
MVP		0.82
MPC		0.71
ClinPred		0.13	T
GERP RS		3.8
Varity_R		0.27
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00074
dbscSNV1_RF	Benign	0.0020
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.

Other links and lift over

hg19: chr1-32741938;