chr20-32052425-C-T

Variant names:

• chr20-32052425-C-T
• ENST00000520553.5:c.-63C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001172132.3(HCK):​c.-126C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCK NM_001172132.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.14
• Publications: 0 publications found

Genes affected

HCK (HGNC:4840): (HCK proto-oncogene, Src family tyrosine kinase) The protein encoded by this gene is a member of the Src family of tyrosine kinases. This protein is primarily hemopoietic, particularly in cells of the myeloid and B-lymphoid lineages. It may help couple the Fc receptor to the activation of the respiratory burst. In addition, it may play a role in neutrophil migration and in the degranulation of neutrophils. Multiple isoforms with different subcellular distributions are produced due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) codon. [provided by RefSeq, Feb 2010]

HCK Gene-Disease associations (from GenCC):

• autoinflammation with pulmonary and cutaneous vasculitis

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 20-32052425-C-T is Benign according to our data. Variant chr20-32052425-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3251251.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172132.3. 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
	HCK	NM_002110.5	MANE Select	c.1C>T	p.Leu1?	start_retained	Exon 1 of 13	NP_002101.2
	HCK	NM_001172132.3		c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001165603.1	A8K4G3
	HCK	NM_001172129.3		c.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001165600.1	P08631-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCK	ENST00000520553.5	TSL:1	c.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000429848.1	P08631-2
	HCK	ENST00000518730.5	TSL:1	c.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000427757.1	P08631-3
	HCK	ENST00000375852.5	TSL:1 MANE Select	c.1C>T	p.Leu1?	start_retained	Exon 1 of 13	ENSP00000365012.3	P08631-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1131240 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 539900

African (AFR) AF: 0.00 AC: 0 AN: 23176

American (AMR) AF: 0.00 AC: 0 AN: 8636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15100

East Asian (EAS) AF: 0.00 AC: 0 AN: 26692

South Asian (SAS) AF: 0.00 AC: 0 AN: 32218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 938044

Other (OTH) AF: 0.00 AC: 0 AN: 45140

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
PhyloP100		2.1
PromoterAI		-0.058	Neutral
Mutation Taster		=288/12	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

hg19: chr20-30640228;