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rs56003471

chr3-195884917-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001382273.1(TNK2):c.351C>T(p.Leu117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,064 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.788
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 -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-195884917-G-A is Benign according to our data. Variant chr3-195884917-G-A is described in ClinVar as [Benign]. Clinvar id is 259880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.788 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1684/152338) while in subpopulation AFR AF= 0.0388 (1612/41568). AF 95% confidence interval is 0.0372. There are 25 homozygotes in gnomad4. There are 825 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1684 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNK2NM_001382273.1 linkuse as main transcriptc.351C>T p.Leu117= synonymous_variant 4/16 ENST00000672887.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNK2ENST00000672887.2 linkuse as main transcriptc.351C>T p.Leu117= synonymous_variant 4/16 NM_001382273.1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0111
AC:
1684
AN:
152220
Hom.:
25
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0388
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00379
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00263
AC:
659
AN:
250726
Hom.:
9
AF XY:
0.00196
AC XY:
266
AN XY:
135670
show subpopulations
Gnomad AFR exome
AF:
0.0377
Gnomad AMR exome
AF:
0.00116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000818
GnomAD4 exome
AF:
0.00109
AC:
1589
AN:
1461726
Hom.:
32
Cov.:
31
AF XY:
0.000931
AC XY:
677
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0399
Gnomad4 AMR exome
AF:
0.00152
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00250
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0111
AC:
1684
AN:
152338
Hom.:
25
Cov.:
33
AF XY:
0.0111
AC XY:
825
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0388
Gnomad4 AMR
AF:
0.00372
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00436
Hom.:
9
Bravo
AF:
0.0128
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 18, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
8.7
Dann
Benign
0.75

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.

Other links and lift over

dbSNP: rs56003471; hg19: chr3-195611788; API