7-3301755-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152744.4(SDK1):c.169A>C(p.Thr57Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: SDK1 NM_152744.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0810

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-AS1 (HGNC:40883): (SDK1 antisense RNA 1)

ACMG classification

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=0.0733217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4	c.169A>C	p.Thr57Pro	missense_variant	1/45	ENST00000404826.7
SDK1-AS1	XR_001744897.3	n.49857+474T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7	c.169A>C	p.Thr57Pro	missense_variant	1/45	1	NM_152744.4	P2
SDK1-AS1	ENST00000437354.1	n.224+474T>G		intron_variant, non_coding_transcript_variant		3
SDK1	ENST00000389531.7	c.169A>C	p.Thr57Pro	missense_variant	1/44	5		A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141152 Hom.: 0 Cov.: 29 FAILED QC

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 141152 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 68586

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.169A>C (p.T57P) 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 169, causing the threonine (T) at amino acid position 57 to be replaced by a proline (P). 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	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	12
Dann	Benign	0.42
DEOGEN2	Benign	0.026	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.26	T;T;T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.27	N;N;.
REVEL	Benign	0.020
Sift	Benign	0.060	T;T;.
Polyphen		0.0080	B;.;.
Vest4		0.15
MutPred		0.15		Loss of phosphorylation at T57 (P = 0.0134);Loss of phosphorylation at T57 (P = 0.0134);Loss of phosphorylation at T57 (P = 0.0134);
MVP		0.34
MPC		0.24
ClinPred		0.067	T
GERP RS		-2.1
Varity_R		0.092
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-3341387;