chr7-3301797-C-T

Variant names:

• chr7-3301797-C-T
• rs891076876
• NM_152744.4:c.211C>T

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.211C>T​(p.Arg71Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,033,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: SDK1 NM_152744.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.699
• 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=0.18587723).

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.211C>T	p.Arg71Trp	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.211C>T	p.Arg71Trp	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
	SDK1	ENST00000389531.7	TSL:5	c.211C>T	p.Arg71Trp	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
	SDK1-AS1	ENST00000437354.2	TSL:3	n.224+432G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000685 AC: 1 AN: 145954 Hom.: 0 Cov.: 31

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000113 AC: 1 AN: 887516 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 414158

African (AFR) AF: 0.00 AC: 0 AN: 17042

American (AMR) AF: 0.00 AC: 0 AN: 2666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6740

East Asian (EAS) AF: 0.00 AC: 0 AN: 7388

South Asian (SAS) AF: 0.00 AC: 0 AN: 17764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1896

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 797536

Other (OTH) AF: 0.00 AC: 0 AN: 30622

GnomAD4 genome AF: 0.00000685 AC: 1 AN: 145954 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 70984

African (AFR) AF: 0.00 AC: 0 AN: 40654

American (AMR) AF: 0.00 AC: 0 AN: 14754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4956

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65678

Other (OTH) AF: 0.00 AC: 0 AN: 2010

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.28
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.70
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.037
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.035	D
Polyphen		0.62	P
Vest4		0.16
MutPred		0.50		Gain of sheet (P = 0.0073)
MVP		0.25
MPC		0.071
ClinPred		0.31	T
GERP RS		0.48
PromoterAI		-0.0072	Neutral
Varity_R		0.074
gMVP		0.19
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: rs891076876; hg19: chr7-3341429;