Variant 7-3301726-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152744.4(SDK1):c.140A>C(p.Glu47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 975,212 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.572

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:):

SDK1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012784541).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4 linkuse as main transcript	c.140A>C	p.Glu47Ala	missense_variant	1/45	ENST00000404826.7	NP_689957.3	Q7Z5N4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SDK1	ENST00000404826.7 linkuse as main transcript	c.140A>C	p.Glu47Ala	missense_variant	1/45	1	NM_152744.4	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7 linkuse as main transcript	c.140A>C	p.Glu47Ala	missense_variant	1/44	5		ENSP00000374182.3	F8W6X9
SDK1-AS1	ENST00000437354.1 linkuse as main transcript	n.224+503T>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

248

AN:

143568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000822

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:

0.0000462

Gnomad OTH

AF:

0.00102

GnomAD4 exome

AF:

0.000121

AC:

101

AN:

831612

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

384090

show subpopulations

Gnomad4 AFR exome

AF:

0.00559

Gnomad4 AMR exome

AF:

0.00100

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:

0.00

Gnomad4 OTH exome

AF:

0.000440

GnomAD4 genome

AF:

0.00175

AC:

251

AN:

143600

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

117

AN XY:

69836

show subpopulations

Gnomad4 AFR

AF:

0.00586

Gnomad4 AMR

AF:

0.000821

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000462

Gnomad4 OTH

AF:

0.00101

Alfa

AF:

0.000996

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.140A>C (p.E47A) alteration is located in exon 1 (coding exon 1) of the SDK1 gene. This alteration results from a A to C substitution at nucleotide position 140, causing the glutamic acid (E) at amino acid position 47 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.85

DEOGEN2

Benign

0.034

T;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.33

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.14

N;N;.

REVEL

Benign

0.037

Sift

Pathogenic

0.0

D;T;.

Polyphen

0.0

B;.;.

Vest4

0.076

MutPred

0.23

Gain of methylation at R43 (P = 0.0523);Gain of methylation at R43 (P = 0.0523);Gain of methylation at R43 (P = 0.0523);

MVP

0.27

MPC

0.14

ClinPred

0.10

GERP RS

-4.1

Varity_R

0.079

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over