7-3301754-G-T

Variant summary

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

The NM_152744.4(SDK1):c.168G>T(p.Glu56Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 983,744 control chromosomes in the GnomAD database, including 10 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E56A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00043 ( 3 hom., cov: 29)

Exomes 𝑓: 0.00032 ( 7 hom. )

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071586072).

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4 linkuse as main transcript	c.168G>T	p.Glu56Asp	missense_variant	1/45	ENST00000404826.7
SDK1-AS1	XR_001744897.3 linkuse as main transcript	n.49857+475C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7 linkuse as main transcript	c.168G>T	p.Glu56Asp	missense_variant	1/45	1	NM_152744.4	P2	Q7Z5N4-1
SDK1-AS1	ENST00000437354.1 linkuse as main transcript	n.224+475C>A		intron_variant, non_coding_transcript_variant		3
SDK1	ENST00000389531.7 linkuse as main transcript	c.168G>T	p.Glu56Asp	missense_variant	1/44	5		A2

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

145216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000320

AC:

268

AN:

838482

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

135

AN XY:

387872

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:

0.0137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000392

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000427

AC:

AN:

145262

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

AN XY:

70652

show subpopulations

Gnomad4 AFR

AF:

0.0000491

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.0125

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000529

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

Jul 05, 2022

The c.168G>T (p.E56D) alteration is located in exon 1 (coding exon 1) of the SDK1 gene. This alteration results from a G to T substitution at nucleotide position 168, causing the glutamic acid (E) at amino acid position 56 to be replaced by an aspartic acid (D). 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

0.096

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.026

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.37

T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.16

N;N;.

REVEL

Benign

0.044

Sift

Benign

0.14

T;T;.

Polyphen

0.0050

B;.;.

Vest4

0.067

MutPred

0.12

Gain of glycosylation at T57 (P = 0.1109);Gain of glycosylation at T57 (P = 0.1109);Gain of glycosylation at T57 (P = 0.1109);

MVP

0.47

MPC

0.11

ClinPred

0.065

GERP RS

1.5

Varity_R

0.087

gMVP

0.097

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