Genetic Variant HCK:p.Asn64Asn (chr20-32073327-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002110.5(HCK):c.192T>C(p.Asn64Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00837 in 1,611,380 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 66 hom. )

Consequence

HCK
NM_002110.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.210

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 20-32073327-T-C is Benign according to our data. Variant chr20-32073327-T-C is described in ClinVar as [Benign]. Clinvar id is 3239003.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.21 with no splicing effect.

BS2

High AC in GnomAd4 at 1546 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCK	NM_002110.5 link	c.192T>C	p.Asn64Asn	synonymous_variant	Exon 3 of 13	ENST00000375852.5	NP_002101.2	P08631-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCK	ENST00000375852.5 link	c.192T>C	p.Asn64Asn	synonymous_variant	Exon 3 of 13	1	NM_002110.5	ENSP00000365012.3		P08631-1J3KPD6

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1542

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00958

GnomAD3 exomes

AF:

0.00985

AC:

2450

AN:

248820

Hom.:

AF XY:

0.00951

AC XY:

1280

AN XY:

134656

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.00833

Gnomad ASJ exome

AF:

0.0206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.00819

AC:

11943

AN:

1459130

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

5855

AN XY:

726034

show subpopulations

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.00870

Gnomad4 ASJ exome

AF:

0.0197

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00338

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.00789

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.0102

AC:

1546

AN:

152250

Hom.:

Cov.:

AF XY:

0.00997

AC XY:

742

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.00816

Gnomad4 OTH

AF:

0.00948

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0107

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00997

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HCK: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.6

DANN

Benign

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over