Variant chr7-3301728-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152744.4(SDK1):c.142C>A(p.Pro48Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 977,352 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.022 ( 130 hom., cov: 29)

Exomes 𝑓: 0.0020 ( 65 hom. )

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.58

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029640496).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4 linkuse as main transcript	c.142C>A	p.Pro48Thr	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.142C>A	p.Pro48Thr	missense_variant	1/45	1	NM_152744.4	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7 linkuse as main transcript	c.142C>A	p.Pro48Thr	missense_variant	1/44	5		ENSP00000374182.3	F8W6X9
SDK1-AS1	ENST00000437354.1 linkuse as main transcript	n.224+501G>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3258

AN:

145166

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00803

Gnomad ASJ

AF:

0.00148

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00671

Gnomad NFE

AF:

0.000352

Gnomad OTH

AF:

0.0185

GnomAD4 exome

AF:

0.00201

AC:

1674

AN:

832150

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

727

AN XY:

384350

show subpopulations

Gnomad4 AFR exome

AF:

0.0886

Gnomad4 AMR exome

AF:

0.00900

Gnomad4 ASJ exome

AF:

0.00136

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.0225

AC:

3262

AN:

145202

Hom.:

130

Cov.:

AF XY:

0.0216

AC XY:

1523

AN XY:

70590

show subpopulations

Gnomad4 AFR

AF:

0.0757

Gnomad4 AMR

AF:

0.00802

Gnomad4 ASJ

AF:

0.00148

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000421

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000352

Gnomad4 OTH

AF:

0.0183

Alfa

AF:

0.00118

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

Aug 09, 2021

The c.142C>A (p.P48T) alteration is located in exon 1 (coding exon 1) of the SDK1 gene. This alteration results from a C to A substitution at nucleotide position 142, causing the proline (P) at amino acid position 48 to be replaced by a threonine (T). 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

0.071

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.7

DANN

Benign

0.54

DEOGEN2

Benign

0.025

T;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.37

T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

0.0

N;N;.

REVEL

Benign

0.014

Sift

Benign

0.37

T;T;.

Polyphen

0.0010

B;.;.

Vest4

0.11

MutPred

0.27

Gain of phosphorylation at P48 (P = 0.0017);Gain of phosphorylation at P48 (P = 0.0017);Gain of phosphorylation at P48 (P = 0.0017);

MVP

0.27

MPC

0.27

ClinPred

0.031

GERP RS

-0.35

Varity_R

0.030

gMVP

0.21

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