rs1047846064

Variant names:

• chr7-3301702-C-T
• rs1047846064
• NM_152744.4:c.116C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-3301702-C-T
• chr7-3301702-C-A
• chr7-3301702-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152744.4(SDK1):​c.116C>T​(p.Ser39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 973,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000042 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: SDK1 NM_152744.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08196768).

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.116C>T	p.Ser39Leu	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.116C>T	p.Ser39Leu	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
	SDK1	ENST00000389531.7	TSL:5	c.116C>T	p.Ser39Leu	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
	SDK1-AS1	ENST00000437354.2	TSL:3	n.224+527G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000416 AC: 6 AN: 144198 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000603 AC: 5 AN: 829512 Hom.: 0 Cov.: 26 AF XY: 0.00000522 AC XY: 2 AN XY: 383130

African (AFR) AF: 0.0000637 AC: 1 AN: 15690

American (AMR) AF: 0.00 AC: 0 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5142

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.000244 AC: 4 AN: 16410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 758604

Other (OTH) AF: 0.00 AC: 0 AN: 27184

GnomAD4 genome AF: 0.0000416 AC: 6 AN: 144208 Hom.: 0 Cov.: 29 AF XY: 0.0000143 AC XY: 1 AN XY: 70080

African (AFR) AF: 0.000124 AC: 5 AN: 40270

American (AMR) AF: 0.00 AC: 0 AN: 14656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3374

East Asian (EAS) AF: 0.00 AC: 0 AN: 4844

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65060

Other (OTH) AF: 0.00 AC: 0 AN: 2000

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

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	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.38		Loss of phosphorylation at S39 (P = 0.0011)
MVP		0.43
MPC		0.13
ClinPred		0.13	T
GERP RS		-1.2
PromoterAI		0.018	Neutral
Varity_R		0.063
gMVP		0.15
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: rs1047846064; hg19: chr7-3341334;