NM_002110.5:c.192T>C

Variant names:

• chr20-32073327-T-C
• rs34513177
• NM_002110.5:c.192T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210
• Publications: 4 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: Benign. The variant received -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 VariationId 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,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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCK	NM_002110.5	MANE Select	c.192T>C	p.Asn64Asn	synonymous	Exon 3 of 13	NP_002101.2
	HCK	NM_001172130.3		c.192T>C	p.Asn64Asn	synonymous	Exon 3 of 13	NP_001165601.1	P08631-4
	HCK	NM_001172132.3		c.132T>C	p.Asn44Asn	synonymous	Exon 4 of 14	NP_001165603.1	A8K4G3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCK	ENST00000375852.5	TSL:1 MANE Select	c.192T>C	p.Asn64Asn	synonymous	Exon 3 of 13	ENSP00000365012.3	P08631-1
	HCK	ENST00000375862.7	TSL:1	c.192T>C	p.Asn64Asn	synonymous	Exon 3 of 13	ENSP00000365022.3	P08631-4
	HCK	ENST00000520553.5	TSL:1	c.129T>C	p.Asn43Asn	synonymous	Exon 3 of 13	ENSP00000429848.1	P08631-2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1542 AN: 152132 Hom.: 11 Cov.: 32

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

GnomAD2 exomes AF: 0.00985 AC: 2450 AN: 248820 AF XY: 0.00951

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 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.: 66 Cov.: 30 AF XY: 0.00806 AC XY: 5855 AN XY: 726034

African (AFR) AF: 0.0137 AC: 456 AN: 33270

American (AMR) AF: 0.00870 AC: 382 AN: 43906

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 513 AN: 26020

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.00338 AC: 290 AN: 85886

European-Finnish (FIN) AF: 0.0148 AC: 792 AN: 53394

Middle Eastern (MID) AF: 0.0163 AC: 94 AN: 5762

European-Non Finnish (NFE) AF: 0.00789 AC: 8760 AN: 1110946

Other (OTH) AF: 0.0109 AC: 655 AN: 60286

GnomAD4 genome AF: 0.0102 AC: 1546 AN: 152250 Hom.: 11 Cov.: 32 AF XY: 0.00997 AC XY: 742 AN XY: 74430

African (AFR) AF: 0.0136 AC: 565 AN: 41558

American (AMR) AF: 0.00915 AC: 140 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4820

European-Finnish (FIN) AF: 0.0107 AC: 114 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 68010

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.0103 Hom.: 4

Bravo AF: 0.0107

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.00905

EpiControl AF: 0.00997

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.35
PhyloP100		0.21
Mutation Taster		=100/0	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

dbSNP: rs34513177; hg19: chr20-30661130;