19-40577435-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_138392.4(SHKBP1):​c.180C>T​(p.Thr60Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,459,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SHKBP1
NM_138392.4 synonymous

Scores

8

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.33
Variant links:
Genes affected
SHKBP1 (HGNC:19214): (SH3KBP1 binding protein 1) Enables identical protein binding activity. Predicted to be involved in positive regulation of epidermal growth factor receptor signaling pathway. Predicted to be located in lysosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10847035).
BP6
Variant 19-40577435-C-T is Benign according to our data. Variant chr19-40577435-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3318321.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.33 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHKBP1NM_138392.4 linkc.180C>T p.Thr60Thr synonymous_variant Exon 3 of 18 ENST00000291842.10 NP_612401.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHKBP1ENST00000291842.10 linkc.180C>T p.Thr60Thr synonymous_variant Exon 3 of 18 1 NM_138392.4 ENSP00000291842.4 Q8TBC3-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251340
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135844
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1459114
Hom.:
0
Cov.:
35
AF XY:
0.0000179
AC XY:
13
AN XY:
725882
show subpopulations
Gnomad4 AFR exome
AF:
0.000419
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000996
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jun 10, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
8.7
DANN
Benign
0.93
DEOGEN2
Benign
0.0057
T
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.34
T
MetaRNN
Benign
0.11
T
MVP
0.67
GERP RS
-9.1

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: rs751960106; hg19: chr19-41083341; COSMIC: COSV52539604; COSMIC: COSV52539604; API