Genetic Variant SHCBP1:p.Glu586Lys (chr16-46581992-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024745.5(SHCBP1):c.1756G>A(p.Glu586Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SHCBP1
NM_024745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Publications

0 publications found

Variant links:

Genes affected

SHCBP1 (HGNC:29547): (SHC binding and spindle associated 1) Predicted to enable SH2 domain binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway and regulation of neural precursor cell proliferation. Predicted to be located in cytoplasm; midbody; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

SHCBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17901212).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024745.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SHCBP1	NM_024745.5	MANE Select	c.1756G>A	p.Glu586Lys	missense	Exon 13 of 13	NP_079021.4
SHCBP1	NM_001324318.2		c.1642G>A	p.Glu548Lys	missense	Exon 13 of 13	NP_001311247.1
SHCBP1	NM_001324319.2		c.1522G>A	p.Glu508Lys	missense	Exon 12 of 12	NP_001311248.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHCBP1	ENST00000303383.8	TSL:1 MANE Select	c.1756G>A	p.Glu586Lys	missense	Exon 13 of 13	ENSP00000306473.3	Q8NEM2
SHCBP1	ENST00000939745.1		c.1588G>A	p.Glu530Lys	missense	Exon 12 of 12	ENSP00000609804.1
SHCBP1	ENST00000567698.1	TSL:2	n.456G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251216

AF XY:

0.00000737

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.078

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.048

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.81

M_CAP

Benign

0.0025

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

3.8

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.4

REVEL

Benign

0.018

Sift

Benign

0.030

Sift4G

Benign

0.073

Polyphen

0.045

Vest4

0.36

MutPred

0.31

Gain of ubiquitination at E586 (P = 0.0114)

MVP

0.35

MPC

0.29

ClinPred

0.37

GERP RS

4.1

Varity_R

0.12

gMVP

0.50

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over