dbSNP rs1020658052: SDK1:p.Pro78Thr (chr7-3301818-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152744.4(SDK1):c.232C>A(p.Pro78Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 940,266 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P78S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 1 hom. )

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.582

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11069885).

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.232C>A	p.Pro78Thr	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.232C>A	p.Pro78Thr	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7	TSL:5	c.232C>A	p.Pro78Thr	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
SDK1-AS1	ENST00000437354.2	TSL:3	n.224+411G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000128

AC:

AN:

940266

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

441436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18448

American (AMR)

AF:

0.00

AC:

AN:

3970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8556

East Asian (EAS)

AF:

0.00

AC:

AN:

13096

South Asian (SAS)

AF:

0.000493

AC:

AN:

18248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2190

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

831286

Other (OTH)

AF:

0.0000884

AC:

AN:

33926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.58

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.030

REVEL

Benign

0.017

Sift

Benign

0.63

Polyphen

0.043

Vest4

0.13

MutPred

0.39

Loss of glycosylation at P78 (P = 0.0219)

MVP

0.30

MPC

0.27

ClinPred

0.12

GERP RS

-0.12

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.042

gMVP

0.19

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over