7-3301754-G-T

Variant names:

• chr7-3301754-G-T
• rs1459318762
• NM_152744.4:c.168G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 15/22 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. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0071586072).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.168G>T	p.Glu56Asp	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.168G>T	p.Glu56Asp	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
	SDK1	ENST00000389531.7	TSL:5	c.168G>T	p.Glu56Asp	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
	SDK1-AS1	ENST00000437354.2	TSL:3	n.224+475C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 62 AN: 145216 Hom.: 3 Cov.: 29

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.: 7 Cov.: 28 AF XY: 0.000348 AC XY: 135 AN XY: 387872

African (AFR) AF: 0.00 AC: 0 AN: 15834

American (AMR) AF: 0.00 AC: 0 AN: 1198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5252

East Asian (EAS) AF: 0.00 AC: 0 AN: 3838

South Asian (SAS) AF: 0.0137 AC: 236 AN: 17164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1634

European-Non Finnish (NFE) AF: 0.00000392 AC: 3 AN: 765110

Other (OTH) AF: 0.00105 AC: 29 AN: 27606

GnomAD4 genome AF: 0.000427 AC: 62 AN: 145262 Hom.: 3 Cov.: 29 AF XY: 0.000694 AC XY: 49 AN XY: 70652

African (AFR) AF: 0.0000491 AC: 2 AN: 40698

American (AMR) AF: 0.00 AC: 0 AN: 14720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.000203 AC: 1 AN: 4922

South Asian (SAS) AF: 0.0125 AC: 59 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65326

Other (OTH) AF: 0.00 AC: 0 AN: 2018

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000529

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	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.044
Sift	Benign	0.14	T
Polyphen		0.0050	B
Vest4		0.067
MutPred		0.12		Gain of glycosylation at T57 (P = 0.1109)
MVP		0.47
MPC		0.11
ClinPred		0.065	T
GERP RS		1.5
PromoterAI		-0.053	Neutral
Varity_R		0.087
gMVP		0.097
Mutation Taster		=100/0	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: rs1459318762; hg19: chr7-3341386;