7-3301728-C-A

Variant names:

• chr7-3301728-C-A
• rs868254792
• NM_152744.4:c.142C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.58
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

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.142C>A	p.Pro48Thr	missense	Exon 1 of 45	NP_689957.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDK1	ENST00000404826.7	TSL:1 MANE Select	c.142C>A	p.Pro48Thr	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
	SDK1	ENST00000389531.7	TSL:5	c.142C>A	p.Pro48Thr	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
	SDK1-AS1	ENST00000437354.2	TSL:3	n.224+501G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3258 AN: 145166 Hom.: 130 Cov.: 29

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.: 65 Cov.: 28 AF XY: 0.00189 AC XY: 727 AN XY: 384350

African (AFR) AF: 0.0886 AC: 1396 AN: 15750

American (AMR) AF: 0.00900 AC: 9 AN: 1000

Ashkenazi Jewish (ASJ) AF: 0.00136 AC: 7 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3636

South Asian (SAS) AF: 0.000120 AC: 2 AN: 16604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 312

Middle Eastern (MID) AF: 0.00493 AC: 8 AN: 1622

European-Non Finnish (NFE) AF: 0.000185 AC: 141 AN: 760784

Other (OTH) AF: 0.00407 AC: 111 AN: 27290

GnomAD4 genome AF: 0.0225 AC: 3262 AN: 145202 Hom.: 130 Cov.: 29 AF XY: 0.0216 AC XY: 1523 AN XY: 70590

African (AFR) AF: 0.0757 AC: 3075 AN: 40604

American (AMR) AF: 0.00802 AC: 118 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.00148 AC: 5 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4896

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8242

Middle Eastern (MID) AF: 0.00725 AC: 2 AN: 276

European-Non Finnish (NFE) AF: 0.000352 AC: 23 AN: 65412

Other (OTH) AF: 0.0183 AC: 37 AN: 2020

Alfa AF: 0.00118 Hom.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.7
DANN	Benign	0.54
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.014
Sift	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.27		Gain of phosphorylation at P48 (P = 0.0017)
MVP		0.27
MPC		0.27
ClinPred		0.031	T
GERP RS		-0.35
PromoterAI		0.014	Neutral
Varity_R		0.030
gMVP		0.21
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs868254792; hg19: chr7-3341360; COSMIC: COSV67367033;