dbSNP rs1291204042: SDK1:p.Arg52Gln (chr7-3301741-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152744.4(SDK1):c.155G>A(p.Arg52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 979,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.000028 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10915315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4 link	c.155G>A	p.Arg52Gln	missense_variant	Exon 1 of 45	ENST00000404826.7	NP_689957.3	Q7Z5N4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDK1	ENST00000404826.7 link	c.155G>A	p.Arg52Gln	missense_variant	Exon 1 of 45	1	NM_152744.4	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7 link	c.155G>A	p.Arg52Gln	missense_variant	Exon 1 of 44	5		ENSP00000374182.3	F8W6X9
SDK1-AS1	ENST00000437354.1 link	n.224+488C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0000276

AC:

AN:

145132

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:

0.0000612

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

834772

Hom.:

Cov.:

AF XY:

0.00000778

AC XY:

AN XY:

385706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000276

AC:

AN:

145180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70602

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000612

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.025

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.50

T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.19

N;N;.

REVEL

Benign

0.065

Sift

Benign

0.058

T;D;.

Polyphen

0.74

P;.;.

Vest4

0.092

MutPred

0.32

Loss of methylation at R52 (P = 0.0084);Loss of methylation at R52 (P = 0.0084);Loss of methylation at R52 (P = 0.0084);

MVP

0.40

MPC

0.14

ClinPred

0.10

GERP RS

0.42

Varity_R

0.063

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over