Genetic Variant SDK1:p.Ala88Glu (chr7-3301849-C-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_152744.4(SDK1):c.263C>A(p.Ala88Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 149,992 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. A88G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.224

Publications

2 publications found

Variant links:

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

SDK1 links:

SDK1-AS1 (HGNC:40883): (SDK1 antisense RNA 1)

SDK1-AS1 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=0.13558173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152744.4. 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
	SDK1	NM_152744.4	MANE Select	c.263C>A	p.Ala88Glu	missense	Exon 1 of 45	NP_689957.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDK1	ENST00000404826.7	TSL:1 MANE Select	c.263C>A	p.Ala88Glu	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7	TSL:5	c.263C>A	p.Ala88Glu	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
SDK1-AS1	ENST00000437354.2	TSL:3	n.224+380G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

983762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

463276

African (AFR)

AF:

0.00

AC:

AN:

19570

American (AMR)

AF:

0.00

AC:

AN:

5192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10280

East Asian (EAS)

AF:

0.00

AC:

AN:

17840

South Asian (SAS)

AF:

0.00

AC:

AN:

18720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2438

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

858646

Other (OTH)

AF:

0.00

AC:

AN:

36664

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73174

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41164

American (AMR)

AF:

0.00

AC:

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5080

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67388

Other (OTH)

AF:

0.00

AC:

AN:

2058

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.040

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.41

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.22

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.35

REVEL

Benign

0.076

Sift

Benign

0.079

Sift4G

Benign

0.076

Polyphen

0.032

Vest4

0.10

MutPred

0.68

Loss of MoRF binding (P = 0.0696)

MVP

0.24

MPC

0.086

ClinPred

0.043

GERP RS

-1.0

PromoterAI

0.0089

Neutral

(source)

Varity_R

0.11

gMVP

0.39

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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