Genetic Variant SDK1:p.Arg52Leu (chr7-3301741-G-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_152744.4(SDK1):c.155G>T(p.Arg52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. R52P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

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: 0.0340

Publications

0 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=0.15988886).

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.155G>T	p.Arg52Leu	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.155G>T	p.Arg52Leu	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7	TSL:5	c.155G>T	p.Arg52Leu	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
SDK1-AS1	ENST00000437354.2	TSL:3	n.224+488C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

834772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

385706

African (AFR)

AF:

0.00

AC:

AN:

15784

American (AMR)

AF:

0.00

AC:

AN:

1064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5184

East Asian (EAS)

AF:

0.00

AC:

AN:

3694

South Asian (SAS)

AF:

0.00

AC:

AN:

16876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1624

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

762672

Other (OTH)

AF:

0.00

AC:

AN:

27416

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.025

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.034

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.27

REVEL

Benign

0.019

Sift

Uncertain

0.025

Polyphen

0.39

Vest4

0.12

MutPred

0.33

Loss of methylation at R52 (P = 0.0084)

MVP

0.48

MPC

0.15

ClinPred

0.13

GERP RS

0.42

PromoterAI

0.19

Neutral

(source)

Varity_R

0.14

gMVP

0.23

Mutation Taster

=100/0

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

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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