Genetic Variant SDCBP:p.Val96Ile (chr8-58575945-G-A) – 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_005625.4(SDCBP):c.286G>A(p.Val96Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V96L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDCBP
NM_005625.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.33

Publications

0 publications found

Variant links:

Genes affected

SDCBP (HGNC:10662): (syndecan binding protein) The protein encoded by this gene was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton. The syntenin protein contains tandemly repeated PDZ domains that bind the cytoplasmic, C-terminal domains of a variety of transmembrane proteins. This protein may also affect cytoskeletal-membrane organization, cell adhesion, protein trafficking, and the activation of transcription factors. The protein is primarily localized to membrane-associated adherens junctions and focal adhesions but is also found at the endoplasmic reticulum and nucleus. Alternative splicing results in multiple transcript variants encoding different isoforms. Related pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Jan 2017]

SDCBP 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=0.12918243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDCBP	NM_005625.4	MANE Select	c.286G>A	p.Val96Ile	missense	Exon 5 of 9	NP_005616.2	O00560-1
SDCBP	NM_001348341.2		c.349G>A	p.Val117Ile	missense	Exon 6 of 10	NP_001335270.1
SDCBP	NM_001330537.2		c.346G>A	p.Val116Ile	missense	Exon 6 of 10	NP_001317466.1	G5EA09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDCBP	ENST00000260130.9	TSL:1 MANE Select	c.286G>A	p.Val96Ile	missense	Exon 5 of 9	ENSP00000260130.4	O00560-1
SDCBP	ENST00000447182.6	TSL:1	c.283G>A	p.Val95Ile	missense	Exon 5 of 9	ENSP00000409288.2	O00560-2
SDCBP	ENST00000523483.5	TSL:2	c.346G>A	p.Val116Ile	missense	Exon 6 of 10	ENSP00000428184.1	G5EA09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461186

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111526

Other (OTH)

AF:

0.0000166

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

3.3

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.070

REVEL

Benign

0.028

Sift

Benign

0.26

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.096

MutPred

0.35

Loss of phosphorylation at T117 (P = 0.1705)

MVP

0.072

MPC

0.23

ClinPred

0.74

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.19

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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