chr3-195888505-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382273.1(TNK2):ā€‹c.84T>Cā€‹(p.Asp28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,612,956 control chromosomes in the GnomAD database, including 79,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.39 ( 12905 hom., cov: 30)
Exomes š‘“: 0.29 ( 66213 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.789
Variant links:
Genes affected
TNK2 (HGNC:19297): (tyrosine kinase non receptor 2) This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 3-195888505-A-G is Benign according to our data. Variant chr3-195888505-A-G is described in ClinVar as [Benign]. Clinvar id is 259882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.789 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNK2NM_001382273.1 linkuse as main transcriptc.84T>C p.Asp28= synonymous_variant 2/16 ENST00000672887.2 NP_001369202.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNK2ENST00000672887.2 linkuse as main transcriptc.84T>C p.Asp28= synonymous_variant 2/16 NM_001382273.1 ENSP00000499899

Frequencies

GnomAD3 genomes
AF:
0.388
AC:
58818
AN:
151702
Hom.:
12883
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.603
Gnomad AMI
AF:
0.253
Gnomad AMR
AF:
0.387
Gnomad ASJ
AF:
0.406
Gnomad EAS
AF:
0.441
Gnomad SAS
AF:
0.304
Gnomad FIN
AF:
0.290
Gnomad MID
AF:
0.377
Gnomad NFE
AF:
0.275
Gnomad OTH
AF:
0.369
GnomAD3 exomes
AF:
0.337
AC:
84585
AN:
250728
Hom.:
15392
AF XY:
0.329
AC XY:
44618
AN XY:
135524
show subpopulations
Gnomad AFR exome
AF:
0.611
Gnomad AMR exome
AF:
0.387
Gnomad ASJ exome
AF:
0.410
Gnomad EAS exome
AF:
0.441
Gnomad SAS exome
AF:
0.303
Gnomad FIN exome
AF:
0.296
Gnomad NFE exome
AF:
0.278
Gnomad OTH exome
AF:
0.326
GnomAD4 exome
AF:
0.294
AC:
428921
AN:
1461136
Hom.:
66213
Cov.:
36
AF XY:
0.292
AC XY:
212434
AN XY:
726840
show subpopulations
Gnomad4 AFR exome
AF:
0.608
Gnomad4 AMR exome
AF:
0.391
Gnomad4 ASJ exome
AF:
0.413
Gnomad4 EAS exome
AF:
0.428
Gnomad4 SAS exome
AF:
0.302
Gnomad4 FIN exome
AF:
0.293
Gnomad4 NFE exome
AF:
0.270
Gnomad4 OTH exome
AF:
0.328
GnomAD4 genome
AF:
0.388
AC:
58893
AN:
151820
Hom.:
12905
Cov.:
30
AF XY:
0.387
AC XY:
28724
AN XY:
74174
show subpopulations
Gnomad4 AFR
AF:
0.603
Gnomad4 AMR
AF:
0.388
Gnomad4 ASJ
AF:
0.406
Gnomad4 EAS
AF:
0.441
Gnomad4 SAS
AF:
0.303
Gnomad4 FIN
AF:
0.290
Gnomad4 NFE
AF:
0.275
Gnomad4 OTH
AF:
0.369
Alfa
AF:
0.307
Hom.:
14593
Bravo
AF:
0.409
Asia WGS
AF:
0.411
AC:
1428
AN:
3478
EpiCase
AF:
0.300
EpiControl
AF:
0.297

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.89
DANN
Benign
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs3747669; hg19: chr3-195615376; COSMIC: COSV57376334; COSMIC: COSV57376334; API