Genetic Variant HCK:p.Pro71Gln (chr20-32073347-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002110.5(HCK):c.212C>A(p.Pro71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

HCK
NM_002110.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.681

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autoinflammation with pulmonary and cutaneous vasculitis
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

HCK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13823116).

BS2

High AC in GnomAd4 at 5 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HCK	NM_002110.5	MANE Select	c.212C>A	p.Pro71Gln	missense	Exon 3 of 13	NP_002101.2
HCK	NM_001172130.3		c.212C>A	p.Pro71Gln	missense	Exon 3 of 13	NP_001165601.1	P08631-4
HCK	NM_001172132.3		c.152C>A	p.Pro51Gln	missense	Exon 4 of 14	NP_001165603.1	A8K4G3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HCK	ENST00000375852.5	TSL:1 MANE Select	c.212C>A	p.Pro71Gln	missense	Exon 3 of 13	ENSP00000365012.3	P08631-1
HCK	ENST00000375862.7	TSL:1	c.212C>A	p.Pro71Gln	missense	Exon 3 of 13	ENSP00000365022.3	P08631-4
HCK	ENST00000520553.5	TSL:1	c.149C>A	p.Pro50Gln	missense	Exon 3 of 13	ENSP00000429848.1	P08631-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249518

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459750

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33338

American (AMR)

AF:

0.00

AC:

AN:

44068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

85942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111256

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.026

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.40

M_CAP

Benign

0.032

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.4

PhyloP100

0.68

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.30

Sift

Uncertain

0.025

Sift4G

Uncertain

0.034

Polyphen

0.0

Vest4

0.37

MVP

0.80

ClinPred

0.13

GERP RS

3.3

Varity_R

0.095

gMVP

0.24

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over