dbSNP rs2081217072: SHKBP1:p.Pro17His (chr19-40576949-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_138392.4(SHKBP1):c.50C>A(p.Pro17His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,986 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SHKBP1
NM_138392.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Publications

0 publications found

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]

SHKBP1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

SHKBP1 links:

ENSG00000301801 (HGNC:):

ENSG00000301801 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28647065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138392.4. 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
	SHKBP1	NM_138392.4	MANE Select	c.50C>A	p.Pro17His	missense	Exon 1 of 18	NP_612401.2	Q8TBC3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHKBP1	ENST00000291842.10	TSL:1 MANE Select	c.50C>A	p.Pro17His	missense	Exon 1 of 18	ENSP00000291842.4	Q8TBC3-1
SHKBP1	ENST00000943564.1		c.50C>A	p.Pro17His	missense	Exon 1 of 19	ENSP00000613623.1
SHKBP1	ENST00000869177.1		c.50C>A	p.Pro17His	missense	Exon 1 of 18	ENSP00000539236.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1350520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664108

African (AFR)

AF:

0.00

AC:

AN:

28908

American (AMR)

AF:

0.00

AC:

AN:

22644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20576

East Asian (EAS)

AF:

0.00

AC:

AN:

35554

South Asian (SAS)

AF:

0.00

AC:

AN:

70668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062402

Other (OTH)

AF:

0.00

AC:

AN:

55322

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41376

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:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

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

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

M_CAP

Benign

0.026

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.3

PhyloP100

2.7

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.4

REVEL

Benign

0.079

Sift4G

Uncertain

0.025

Polyphen

1.0

Vest4

0.42

MutPred

0.23

Loss of glycosylation at P17 (P = 0.0233)

MVP

0.59

MPC

2.4

ClinPred

0.97

GERP RS

4.5

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.60

gMVP

0.52

Mutation Taster

=88/12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over